Pub Date : 2023-06-01DOI: 10.15789/1563-0625-eoe-2663
А. P. Lykov, S. Belogorodtsev, Е. К. Nemkova, А. Vetlugina, Т. М. Terekhova, Y. Schwartz
Innate immune cells (monocytes/macrophages, NK) can also develop immune memory, which means that these cells are trained after their first encounter with pathogens so that they exhibit a nonspecific immunological response to the same or another pathogen. Bacilli Calmette–Gu rin (BCG) induces nonspecific innate memory (trained immunity) in innate immune cells. We examined nonspecific innate memory in macrophages of BALB/c mice in response to mycobacteria with or without the RD1 region in the genome. Mice were immunized with BCG vaccine, and peritoneal macrophages were isolated on day 7, and then stimulated with bacterial lipopolysaccharide, CFP-10, or ESAT-6. In addition, mice were immunized with Mycobacterium tuberculosis uro-BCG vaccine (RD1-) and Mycobacterium tuberculosis strain H37Rv (RD1+) subcutaneously or intravenously; peritoneal macrophages were isolated and stimulated with lipopolysaccharide on day 4. Alveolar macrophages were obtained from lung explants of mice infected with Mycobacterium tuberculosis strain H37Rv mice, were expanded to confluence 70-80% and further stimulated with lipopolysaccharide. Lactate, cytokines, and glucose levels were examined in conditioned macrophage medium. Peritoneal macrophages from mice primed with BCG vaccine were shown to increase IL-1b, TNFa, and lactate production in response to CFP-6 and ESAT-10 (p < 0.05). Of note is the fact that lipopolysaccharide also increased production of IL-1b, TNFa, and also increased glucose uptake by peritoneal macrophages primed with BCG vaccine (p < 0.05). Peritoneal macrophages primed with Uro-BCG were shown to increase spontaneous production of IL-1b and decrease spontaneous production of TNFa (p < 0.05). When macrophages were primed by subcutaneous or intravenous administration of Mycobacterium tuberculosis strain H37Rv differentially affected cytokine production, by decreasing IL-1b production and increasing TNFa and IL-10, was observed. In response to lipopolysaccharide, peritoneal macrophages increased IL-1b, TNFa, IL-10 production and glucose consumption (p < 0.05). The mode of priming of macrophages with Mycobacterium tuberculosis strain H37Rv also led to multidirectional levels of cytokine production. Alveolar macrophages were shown to retain trained immunity, as they produced elevated levels of IL-1b, TNFa, and IL-10 (p < 0.05). Thus, mouse macrophages formed a trained immunity phenotype in response to different types of mycobacteria, which persists for a long time after primary contact with the pathogen, particularly in alveolar macrophages.
{"title":"Effect of CFP-10/ESAT-6 secretory proteins on long-term non-specific immunological memory in mouse macrophages","authors":"А. P. Lykov, S. Belogorodtsev, Е. К. Nemkova, А. Vetlugina, Т. М. Terekhova, Y. Schwartz","doi":"10.15789/1563-0625-eoe-2663","DOIUrl":"https://doi.org/10.15789/1563-0625-eoe-2663","url":null,"abstract":"Innate immune cells (monocytes/macrophages, NK) can also develop immune memory, which means that these cells are trained after their first encounter with pathogens so that they exhibit a nonspecific immunological response to the same or another pathogen. Bacilli Calmette–Gu rin (BCG) induces nonspecific innate memory (trained immunity) in innate immune cells. We examined nonspecific innate memory in macrophages of BALB/c mice in response to mycobacteria with or without the RD1 region in the genome. Mice were immunized with BCG vaccine, and peritoneal macrophages were isolated on day 7, and then stimulated with bacterial lipopolysaccharide, CFP-10, or ESAT-6. In addition, mice were immunized with Mycobacterium tuberculosis uro-BCG vaccine (RD1-) and Mycobacterium tuberculosis strain H37Rv (RD1+) subcutaneously or intravenously; peritoneal macrophages were isolated and stimulated with lipopolysaccharide on day 4. Alveolar macrophages were obtained from lung explants of mice infected with Mycobacterium tuberculosis strain H37Rv mice, were expanded to confluence 70-80% and further stimulated with lipopolysaccharide. Lactate, cytokines, and glucose levels were examined in conditioned macrophage medium. Peritoneal macrophages from mice primed with BCG vaccine were shown to increase IL-1b, TNFa, and lactate production in response to CFP-6 and ESAT-10 (p < 0.05). Of note is the fact that lipopolysaccharide also increased production of IL-1b, TNFa, and also increased glucose uptake by peritoneal macrophages primed with BCG vaccine (p < 0.05). Peritoneal macrophages primed with Uro-BCG were shown to increase spontaneous production of IL-1b and decrease spontaneous production of TNFa (p < 0.05). When macrophages were primed by subcutaneous or intravenous administration of Mycobacterium tuberculosis strain H37Rv differentially affected cytokine production, by decreasing IL-1b production and increasing TNFa and IL-10, was observed. In response to lipopolysaccharide, peritoneal macrophages increased IL-1b, TNFa, IL-10 production and glucose consumption (p < 0.05). The mode of priming of macrophages with Mycobacterium tuberculosis strain H37Rv also led to multidirectional levels of cytokine production. Alveolar macrophages were shown to retain trained immunity, as they produced elevated levels of IL-1b, TNFa, and IL-10 (p < 0.05). Thus, mouse macrophages formed a trained immunity phenotype in response to different types of mycobacteria, which persists for a long time after primary contact with the pathogen, particularly in alveolar macrophages.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86186653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-eoe-2783
Ya. A. Kadochnikova, S. V. Gein
Endogenous opioid peptides are a large group of physiologically active compounds with a pronounced affinity for opioid-type receptors, capable of showing pronounced analgesic activity, as well as having additional effects on the periphery, due to their wide distribution on the cells of many organs and tissues. Little studied representatives of this group are endomorphins, which due to their structure and properties, are capable of producing a strong antinociceptive effect after central administration, which means that, in the future, they can be considered as potential substitutes for low molecular weight opiates. The aim of this study is to evaluate the effect of endomorphins on the humoral immune response, the production of Th1/Th2/Th17 cytokines and apoptosis of CD4+, CD8+ lymphocytes in vivo. The splenocytes of Swiss white mice were used as the object of the study. The number of antibody-forming cells in the spleen was assessed using the method of local hemolysis in agarose gel according to Jerne. Quantitative determination of cytokines was carried out by enzyme-linked immunosorbent assay using kits (R&D, USA) according to the method proposed by the manufacturer. Apoptosis was assessed using Annexin V-FITC/7-AAD kit reagents (Beckman Coulter, USA) according to the manufacturer’s instructions by flow cytometry on a CytoFLEX S flow cytometer (Beckman Coulter, USA). In the course of the study, it was found that endomorphins enhance the antibody genesis of the spleen, and the preliminary blockade of opiate receptors with naloxone led to the cancellation of the stimulating effect of peptides. Endomorphins didn’t affect splenocyte production of IL-2, IL-4, and IFNg, however, the introduction of endomorphin-2 naloxone-independent enhanced the induced production of IL-17. Evaluation of the effect of endomorphins on apoptosis of splenocytes in 24-h cultures showed that endomorphin-2 in unstimulated cultures of naloxone-dependently increased the percentage of late apoptosis of CD8+ lymphocytes, however, in stimulated cultures, both endomorphins increased the apoptotic activity of CD8+ lymphocytes, regardless of the preliminary blockade of opioid receptors. In summary, we can say that in the in vivo system, endomorphins have a wide range of multidirectional immunomodulatory effects, which may be of interest for practical use in the future.
{"title":"Effect of endomorphins on humoral immune response, Th1/Th2/Th17 cytokine production and CD4+, CD8+ lymphocyte apoptosis in vivo","authors":"Ya. A. Kadochnikova, S. V. Gein","doi":"10.15789/1563-0625-eoe-2783","DOIUrl":"https://doi.org/10.15789/1563-0625-eoe-2783","url":null,"abstract":"Endogenous opioid peptides are a large group of physiologically active compounds with a pronounced affinity for opioid-type receptors, capable of showing pronounced analgesic activity, as well as having additional effects on the periphery, due to their wide distribution on the cells of many organs and tissues. Little studied representatives of this group are endomorphins, which due to their structure and properties, are capable of producing a strong antinociceptive effect after central administration, which means that, in the future, they can be considered as potential substitutes for low molecular weight opiates. The aim of this study is to evaluate the effect of endomorphins on the humoral immune response, the production of Th1/Th2/Th17 cytokines and apoptosis of CD4+, CD8+ lymphocytes in vivo. The splenocytes of Swiss white mice were used as the object of the study. The number of antibody-forming cells in the spleen was assessed using the method of local hemolysis in agarose gel according to Jerne. Quantitative determination of cytokines was carried out by enzyme-linked immunosorbent assay using kits (R&D, USA) according to the method proposed by the manufacturer. Apoptosis was assessed using Annexin V-FITC/7-AAD kit reagents (Beckman Coulter, USA) according to the manufacturer’s instructions by flow cytometry on a CytoFLEX S flow cytometer (Beckman Coulter, USA). In the course of the study, it was found that endomorphins enhance the antibody genesis of the spleen, and the preliminary blockade of opiate receptors with naloxone led to the cancellation of the stimulating effect of peptides. Endomorphins didn’t affect splenocyte production of IL-2, IL-4, and IFNg, however, the introduction of endomorphin-2 naloxone-independent enhanced the induced production of IL-17. Evaluation of the effect of endomorphins on apoptosis of splenocytes in 24-h cultures showed that endomorphin-2 in unstimulated cultures of naloxone-dependently increased the percentage of late apoptosis of CD8+ lymphocytes, however, in stimulated cultures, both endomorphins increased the apoptotic activity of CD8+ lymphocytes, regardless of the preliminary blockade of opioid receptors. In summary, we can say that in the in vivo system, endomorphins have a wide range of multidirectional immunomodulatory effects, which may be of interest for practical use in the future.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"105 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80692907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-eoe-2742
R. R. Akhmetyanov, E. Davydova, A. Sabiryanov
Traumatic damage to the anterior cruciate ligament leads to impaired support and mechanical instability of the limb. One of the frequent complications after injury is arthrogenic muscle inhibition due to inhibition of the quadriceps muscle and the development of functional contracture. On the contrary, one of the indicators of high muscle activity is a sufficient level in the blood of functional muscle proteins – myokines, in particular interleukin-6, which are expressed and released by muscle fibers. The aim of the study was to study the level of interleukin-6 in men with damage to the anterior cruciate ligament in the dynamics of electromyostimulation of the quadriceps femoris. The study involved 23 men, mean age 34.8±2.2 years, with traumatic injury of the anterior cruciate ligament, who, 10 days before surgery, underwent electromyostimulation of the quadriceps femoris using the INTELECT® Advanced device (Chattanooga (DJO), USA). The control group consisted of 12 healthy men, mean age 32.2±2.4 years. The level of IL-6 was determined in the blood serum before electromyostimulation, and in dynamics using a kit for enzyme immunoassay (Vector-Best, Novosibirsk). The obtained data were processed using the Statistica licensed software package v. 10.0. The basal level of IL-6 in the main group was 1.28 (0.87-1.72) pg/mL, which is significantly lower than in healthy individuals 5.2 (3.8-6.1) pg/mL and is due to a low level of physical activity due to functional contracture of the quadriceps muscle. In the dynamics of electromyostimulation on the 5th day, the level of IL-6 significantly increased by 3.2 times from the basal level, on the 10th day by 4.6 times, while not exceeding that of the group of healthy individuals. With the reduction of myocytes, the concentration of myokine interleukin-6 increased in the cytoplasm of cells, which contributes to the accumulation of macroergs in the muscle cell, due to myokine-dependent activation of glycogenolysis. The reparative and anti-inflammatory properties of IL-6 are realized in stimulated striated muscles by the classical signaling mechanism that can block the activation of the universal intracellular transcription factor NF-κB in relation to the production of pro-inflammatory cytokines. Thus, electromyostimulation before the start of surgical treatment leads to an increase in the concentration of myokine IL-6 in the blood, which contributes to an increase in the anti-inflammatory and reparative potential of damaged tissues.
{"title":"Effect of electrical stimulation of the thigh muscles on the level of interleukin-6 in traumatic injuries of the anterior cruciate ligament of the knee joint","authors":"R. R. Akhmetyanov, E. Davydova, A. Sabiryanov","doi":"10.15789/1563-0625-eoe-2742","DOIUrl":"https://doi.org/10.15789/1563-0625-eoe-2742","url":null,"abstract":"Traumatic damage to the anterior cruciate ligament leads to impaired support and mechanical instability of the limb. One of the frequent complications after injury is arthrogenic muscle inhibition due to inhibition of the quadriceps muscle and the development of functional contracture. On the contrary, one of the indicators of high muscle activity is a sufficient level in the blood of functional muscle proteins – myokines, in particular interleukin-6, which are expressed and released by muscle fibers. The aim of the study was to study the level of interleukin-6 in men with damage to the anterior cruciate ligament in the dynamics of electromyostimulation of the quadriceps femoris. The study involved 23 men, mean age 34.8±2.2 years, with traumatic injury of the anterior cruciate ligament, who, 10 days before surgery, underwent electromyostimulation of the quadriceps femoris using the INTELECT® Advanced device (Chattanooga (DJO), USA). The control group consisted of 12 healthy men, mean age 32.2±2.4 years. The level of IL-6 was determined in the blood serum before electromyostimulation, and in dynamics using a kit for enzyme immunoassay (Vector-Best, Novosibirsk). The obtained data were processed using the Statistica licensed software package v. 10.0. The basal level of IL-6 in the main group was 1.28 (0.87-1.72) pg/mL, which is significantly lower than in healthy individuals 5.2 (3.8-6.1) pg/mL and is due to a low level of physical activity due to functional contracture of the quadriceps muscle. In the dynamics of electromyostimulation on the 5th day, the level of IL-6 significantly increased by 3.2 times from the basal level, on the 10th day by 4.6 times, while not exceeding that of the group of healthy individuals. With the reduction of myocytes, the concentration of myokine interleukin-6 increased in the cytoplasm of cells, which contributes to the accumulation of macroergs in the muscle cell, due to myokine-dependent activation of glycogenolysis. The reparative and anti-inflammatory properties of IL-6 are realized in stimulated striated muscles by the classical signaling mechanism that can block the activation of the universal intracellular transcription factor NF-κB in relation to the production of pro-inflammatory cytokines. Thus, electromyostimulation before the start of surgical treatment leads to an increase in the concentration of myokine IL-6 in the blood, which contributes to an increase in the anti-inflammatory and reparative potential of damaged tissues.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82022559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-aos-2724
N. S. Chumakov, K. A. Khlystova, N. G. Sarkisyan, F. A. Fadeev, M. M. Mamedov
Modern medicine allows us to study and develop materials and methods of restorative treatment that would be based on the immunological mechanisms of bone repair. One of the promising directions in guided bone regeneration is the use of mesenchymal stem cells. Interest in MSCs is associated with their ability to regulate the inflammatory process, and directly participate in the formation of new bone structures, thereby providing a physiological repair process. The effector impact of MSCs on the inflammatory process due to their ability to form a specific microenvironment. Low expression of MHC-II and CD80/CD86, the production of PGE2 and NO determines their low immunoconflict, and the production of TGF-b1, IDO and IL-10 has an immunomodulating effect. The ability of MSCs to differentiate into an osteogenic phenotype is accompanied with the synthesis of ALP, BSP and, subsequently, Gla-protein and OPN determine the synthesis of the extracellular matrix and its subsequent mineralization. This process is provided by the action of Runx2, which activates the differentiation of MSCs along the osteogenic pathway. These effects of MSCs were taken as the basis for the development of a new method for the treatment of bone atrophy. To accomplish the task set, a model of bone tissue atrophy and a drug containing MSCs was developed, and an experimental study was conducted to evaluate the effectiveness of the developed methodology. As the main criteria, data from clinical and laboratory studies were taken. Visual changes in the studied area were taken into account, compared with a similar area in the developed model of atrophy, the parameters of the complete blood count (CBC) were evaluated. The performed study allows us to determine the developed treatment method as capable of fully recreating the conditions of bone repair processes, taking into account the optimization of the body’s immune reactions and repair processes, without additional external influence, to obtain predictable and controllable results.
{"title":"Application of stem cells in guided bone regeneration","authors":"N. S. Chumakov, K. A. Khlystova, N. G. Sarkisyan, F. A. Fadeev, M. M. Mamedov","doi":"10.15789/1563-0625-aos-2724","DOIUrl":"https://doi.org/10.15789/1563-0625-aos-2724","url":null,"abstract":"Modern medicine allows us to study and develop materials and methods of restorative treatment that would be based on the immunological mechanisms of bone repair. One of the promising directions in guided bone regeneration is the use of mesenchymal stem cells. Interest in MSCs is associated with their ability to regulate the inflammatory process, and directly participate in the formation of new bone structures, thereby providing a physiological repair process. The effector impact of MSCs on the inflammatory process due to their ability to form a specific microenvironment. Low expression of MHC-II and CD80/CD86, the production of PGE2 and NO determines their low immunoconflict, and the production of TGF-b1, IDO and IL-10 has an immunomodulating effect. The ability of MSCs to differentiate into an osteogenic phenotype is accompanied with the synthesis of ALP, BSP and, subsequently, Gla-protein and OPN determine the synthesis of the extracellular matrix and its subsequent mineralization. This process is provided by the action of Runx2, which activates the differentiation of MSCs along the osteogenic pathway. These effects of MSCs were taken as the basis for the development of a new method for the treatment of bone atrophy. To accomplish the task set, a model of bone tissue atrophy and a drug containing MSCs was developed, and an experimental study was conducted to evaluate the effectiveness of the developed methodology. As the main criteria, data from clinical and laboratory studies were taken. Visual changes in the studied area were taken into account, compared with a similar area in the developed model of atrophy, the parameters of the complete blood count (CBC) were evaluated. The performed study allows us to determine the developed treatment method as capable of fully recreating the conditions of bone repair processes, taking into account the optimization of the body’s immune reactions and repair processes, without additional external influence, to obtain predictable and controllable results.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"79 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134904414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-eoa-2728
E. Shevela, N. G. Bukhtueva, M. Tikhonova, L. Sakhno, N. Pasman, E. Chernykh
During pregnancy, the maternal immune system must maintain tolerance to paternal antigens, at the same time being able to eliminate pathogens, which is achieved by the weakening of adoptive immunity and the activation of innate immunity, in particular, monocytes. However, the question about the functional phenotype of monocytes, having not only pro-inflammatory, but also anti-inflammatory activity, remains open. In the given work, we have investigated the expression of M2-associated suppressive markers Arg1 and MerTK in monocyte subpopulations during uncomplicated pregnancy. Fifty-three pregnant women with uncomplicated gestation were recruited, including 14 pregnant in the 1st trimester, 20 – in the 2nd and 19 – in the third pregnancy trimester. The comparison group consisted of 15 fertile unpregnant women without aggravated somatic anamnesis, with a history of at least one childbirth. The findings showed that in the unpregnant group circulating Mo express Arg1 and MerTK, and the most relative number of Arg1+ and MerTK+ cells is concentrated in intermediate and nonclassic monocytes. During pregnancy the expression of researched molecules in monocytes reliably increases. An increase in MerTK expression is manifested by a simultaneous increase in the number of MerTK+ cells and the mean fluorescence intensity of this marker; it is observed in the 1st and 2nd trimesters and registered in all three monocyte subpopulations. At the same time, an increase in Arg1 expression is manifested either by an enhancement of Arg1+ cells, or an increase in receptor density; it is registered throughout pregnancy, including the 3rd trimester, and is maximally expressed in classic monocytes. There is a direct correlation between the number of Arg1+ and MerTK+ cells in intermediate Mo, which increases with the progression of pregnancy, and in the 3rd trimester is also detected in classical and non-classical Mo. In general, the revealed increase in the expression of Arg1 and MerTK by monocytes indicates an increase in the anti-inflammatory potential of monocytes during pregnancy, and the involvement of monocytes in the regulation of the inflammatory process at the system level. Moreover, the features of Arg1 and MerTK expression in various monocyte subpopulations during pregnancy suggest that monocytes expressing Arg1 and MerTK can mediate different mechanisms of immune adaptation during pregnancy.
{"title":"Expression of arginase 1 and tyrosine kinase Mer by blood monocytes in the dynamics of physiological pregnancy","authors":"E. Shevela, N. G. Bukhtueva, M. Tikhonova, L. Sakhno, N. Pasman, E. Chernykh","doi":"10.15789/1563-0625-eoa-2728","DOIUrl":"https://doi.org/10.15789/1563-0625-eoa-2728","url":null,"abstract":"During pregnancy, the maternal immune system must maintain tolerance to paternal antigens, at the same time being able to eliminate pathogens, which is achieved by the weakening of adoptive immunity and the activation of innate immunity, in particular, monocytes. However, the question about the functional phenotype of monocytes, having not only pro-inflammatory, but also anti-inflammatory activity, remains open. In the given work, we have investigated the expression of M2-associated suppressive markers Arg1 and MerTK in monocyte subpopulations during uncomplicated pregnancy. Fifty-three pregnant women with uncomplicated gestation were recruited, including 14 pregnant in the 1st trimester, 20 – in the 2nd and 19 – in the third pregnancy trimester. The comparison group consisted of 15 fertile unpregnant women without aggravated somatic anamnesis, with a history of at least one childbirth. The findings showed that in the unpregnant group circulating Mo express Arg1 and MerTK, and the most relative number of Arg1+ and MerTK+ cells is concentrated in intermediate and nonclassic monocytes. During pregnancy the expression of researched molecules in monocytes reliably increases. An increase in MerTK expression is manifested by a simultaneous increase in the number of MerTK+ cells and the mean fluorescence intensity of this marker; it is observed in the 1st and 2nd trimesters and registered in all three monocyte subpopulations. At the same time, an increase in Arg1 expression is manifested either by an enhancement of Arg1+ cells, or an increase in receptor density; it is registered throughout pregnancy, including the 3rd trimester, and is maximally expressed in classic monocytes. There is a direct correlation between the number of Arg1+ and MerTK+ cells in intermediate Mo, which increases with the progression of pregnancy, and in the 3rd trimester is also detected in classical and non-classical Mo. In general, the revealed increase in the expression of Arg1 and MerTK by monocytes indicates an increase in the anti-inflammatory potential of monocytes during pregnancy, and the involvement of monocytes in the regulation of the inflammatory process at the system level. Moreover, the features of Arg1 and MerTK expression in various monocyte subpopulations during pregnancy suggest that monocytes expressing Arg1 and MerTK can mediate different mechanisms of immune adaptation during pregnancy.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85978675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-pcv-2843
M. A. Urevskii, L. V. Ilmukhina, Ya.E. Saranskaya, A. A. Lapshin, R. R. Gafurova
The mechanism of hepatocellular liver damage after COVID-19 is a multifactorial process. The most widely discussed causes are cytolytic liver damage due to the inflammatory response after COVID-19, drug-induced hepatotoxicity and direct cytotoxic effect of the virus. There are observations that SARSCoV-2 infection causes hepatitis B virus reactivation, but little has been described about the interaction between hepatitis C virus and SARS-CoV-2. The course of coronavirus infection is associated with marked expression of proinflammatory cytokines, participants in the multisystem inflammatory response, IL-1β, IL-6, IL-8, IL-18, MCP-1, TNFα, which contribute significantly to the observed early and late liver function impairment. The aim of the study was to evaluate the role of proinflammatory cytokines (VEGFA, IL-8, IL-6, MCP-1, TNFα, IL-18) as additional markers of hepatotoxicity after COVID-19. The study was performed between March and August 2022. Patients were divided into 2 groups: Group 1 – with increased aminotransferases against the background of treatment from COVID-19 and/or in the following 3-6 months after the disease without viral liver damage (n = 42), Group 2 – patients with co-infection (chronic viral hepatitis C (HCV) and COVID-19 (n = 26). The levels of cytokines – VEGF-A, IL-6, IL-8, MCP-1, IL-18, TNFα in blood serum were estimated by enzyme immunoassay method. Statistical analysis was performed using StatTech v. 3.1.4. The results of the study revealed a comparable increase in the level of transaminases and C-reactive protein in both groups, significantly different from the reference values. Direct correlations of moderate strength (linear Spearman correlation) were found between the following cytokines: TNFα-MCP-1 (R = 0.559; p = 0.001), TNFα-VEGFA (R = 0.400; p = 0.002), TNFα-IL-6 (R = 0.503; p = 0.001). We diagnosed a significant increase in serum VEGFA levels in group 1 patients (hepatotoxicity after COVID-19) (Me (Q0.25-Q0.75): 522 (250 to 1002), p = 0.001) and in group 2 patients (HCV + COVID-19) (Me 1196, Q0.25-Q0.75: (73 to 432). Similar trend with the level of IL-6, IL-8, exceeding the values of cytokines in healthy donors and significantly higher than in group 2 patients. Identified correlations between inflammatory cytokines prove unidirectional changes in the functioning of the regulatory network controlling immune virus-induced reactions.
{"title":"Proinflammatory cytokines VEGFA, IL-6, IL-8 as markers of hepatotoxicity after COVID-19","authors":"M. A. Urevskii, L. V. Ilmukhina, Ya.E. Saranskaya, A. A. Lapshin, R. R. Gafurova","doi":"10.15789/1563-0625-pcv-2843","DOIUrl":"https://doi.org/10.15789/1563-0625-pcv-2843","url":null,"abstract":"The mechanism of hepatocellular liver damage after COVID-19 is a multifactorial process. The most widely discussed causes are cytolytic liver damage due to the inflammatory response after COVID-19, drug-induced hepatotoxicity and direct cytotoxic effect of the virus. There are observations that SARSCoV-2 infection causes hepatitis B virus reactivation, but little has been described about the interaction between hepatitis C virus and SARS-CoV-2. The course of coronavirus infection is associated with marked expression of proinflammatory cytokines, participants in the multisystem inflammatory response, IL-1β, IL-6, IL-8, IL-18, MCP-1, TNFα, which contribute significantly to the observed early and late liver function impairment. The aim of the study was to evaluate the role of proinflammatory cytokines (VEGFA, IL-8, IL-6, MCP-1, TNFα, IL-18) as additional markers of hepatotoxicity after COVID-19. The study was performed between March and August 2022. Patients were divided into 2 groups: Group 1 – with increased aminotransferases against the background of treatment from COVID-19 and/or in the following 3-6 months after the disease without viral liver damage (n = 42), Group 2 – patients with co-infection (chronic viral hepatitis C (HCV) and COVID-19 (n = 26). The levels of cytokines – VEGF-A, IL-6, IL-8, MCP-1, IL-18, TNFα in blood serum were estimated by enzyme immunoassay method. Statistical analysis was performed using StatTech v. 3.1.4. The results of the study revealed a comparable increase in the level of transaminases and C-reactive protein in both groups, significantly different from the reference values. Direct correlations of moderate strength (linear Spearman correlation) were found between the following cytokines: TNFα-MCP-1 (R = 0.559; p = 0.001), TNFα-VEGFA (R = 0.400; p = 0.002), TNFα-IL-6 (R = 0.503; p = 0.001). We diagnosed a significant increase in serum VEGFA levels in group 1 patients (hepatotoxicity after COVID-19) (Me (Q0.25-Q0.75): 522 (250 to 1002), p = 0.001) and in group 2 patients (HCV + COVID-19) (Me 1196, Q0.25-Q0.75: (73 to 432). Similar trend with the level of IL-6, IL-8, exceeding the values of cytokines in healthy donors and significantly higher than in group 2 patients. Identified correlations between inflammatory cytokines prove unidirectional changes in the functioning of the regulatory network controlling immune virus-induced reactions.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87621586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-aot-2737
Z. Buzitskaya, A. Popov, E. Romanovskaya-Romanko, M. Sergeeva, E. Varyushina, M. K. Erofeeva, M. Stukova, D. Lioznov
Causing millions of cases worldwide every year, influenza is one of the most common respiratory infections. The effectiveness of influenza vaccination and the nature of the resulting immune response may vary depending on the vaccine composition and age group. Since children are at the highest risk of disease and act as the main carriers of influenza, the assessment of the immunological efficacy of vaccines in this group is crucial for controlling the epidemic. Therefore, this study aimed to evaluate the characteristics of the humoral immune response in children after immunization with various types of inactivated influenza vaccines. An observational study was conducted in the 2019-2020 season and involved 230 children (< 18 years old) and a comparison group of 87 adults aged 18 to 60 years. The subjects, who provided informed consent to participate, were vaccinated with one of three vaccines (Grippol Plus, Sovigripp, or Ultrix) in an open-label fashion. The humoral immune response was assessed by measuring the hemagglutination inhibition (HI) titer in the paired sera taken before and three weeks after vaccination. The immunogenicity of the vaccines in the age group under 18, met the CPMP criteria for the assessment of inactivated influenza vaccines in terms of the fold increase in antibody titers and the proportion of individuals with seroconversion to all three components (A/H1N1pdm09, A/H3N2, and B/Victoria). Although 6 to 18-year-old participants showed a more robust immune response to the B/Victoria component compared to the adult participants (aged 18 to 60), it was insufficient to ensure that 70% of the participants have a protective antibody titer. A comparative analysis of the vaccines’ immunogenicity was carried out for a subgroup of children aged 6-18 who had initially low antibody levels at the time of vaccination. The analysis showed that the split vaccine Ultrix outperformed the adjuvanted vaccine Grippol Plus in generating an antibody response to the component B/Victoria; however, the antibody responses to the A/H1N1pdm09 and A/H3N2 components did not differ between the two vaccines. The children under 6 years of age demonstrated a less pronounced humoral immune response to vaccination compared with the other age groups, which may be due to the age-related characteristics of the immune system in children of preschool age.
{"title":"Assessment of the humoral immune response in children after immunization with different types of inactivated influenza vaccines in the 2019-2020 season","authors":"Z. Buzitskaya, A. Popov, E. Romanovskaya-Romanko, M. Sergeeva, E. Varyushina, M. K. Erofeeva, M. Stukova, D. Lioznov","doi":"10.15789/1563-0625-aot-2737","DOIUrl":"https://doi.org/10.15789/1563-0625-aot-2737","url":null,"abstract":"Causing millions of cases worldwide every year, influenza is one of the most common respiratory infections. The effectiveness of influenza vaccination and the nature of the resulting immune response may vary depending on the vaccine composition and age group. Since children are at the highest risk of disease and act as the main carriers of influenza, the assessment of the immunological efficacy of vaccines in this group is crucial for controlling the epidemic. Therefore, this study aimed to evaluate the characteristics of the humoral immune response in children after immunization with various types of inactivated influenza vaccines. An observational study was conducted in the 2019-2020 season and involved 230 children (< 18 years old) and a comparison group of 87 adults aged 18 to 60 years. The subjects, who provided informed consent to participate, were vaccinated with one of three vaccines (Grippol Plus, Sovigripp, or Ultrix) in an open-label fashion. The humoral immune response was assessed by measuring the hemagglutination inhibition (HI) titer in the paired sera taken before and three weeks after vaccination. The immunogenicity of the vaccines in the age group under 18, met the CPMP criteria for the assessment of inactivated influenza vaccines in terms of the fold increase in antibody titers and the proportion of individuals with seroconversion to all three components (A/H1N1pdm09, A/H3N2, and B/Victoria). Although 6 to 18-year-old participants showed a more robust immune response to the B/Victoria component compared to the adult participants (aged 18 to 60), it was insufficient to ensure that 70% of the participants have a protective antibody titer. A comparative analysis of the vaccines’ immunogenicity was carried out for a subgroup of children aged 6-18 who had initially low antibody levels at the time of vaccination. The analysis showed that the split vaccine Ultrix outperformed the adjuvanted vaccine Grippol Plus in generating an antibody response to the component B/Victoria; however, the antibody responses to the A/H1N1pdm09 and A/H3N2 components did not differ between the two vaccines. The children under 6 years of age demonstrated a less pronounced humoral immune response to vaccination compared with the other age groups, which may be due to the age-related characteristics of the immune system in children of preschool age.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"AES-13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84544218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-iom-2842
А. Р. Godovalov, I. A. Morozov
As is known, bacterial polyamines, which include cadaverine and putrescine, are capable of influencing the activity of immunocompetent cells in many ways. In particular, this situation is observed in long-term inflammatory diseases, especially with intensive reproduction of microorganisms capable of producing polyamines. It is of interest to study the production of one of the main anti-inflammatory cytokines, IL-10, under the influence of bacterial polyamines. For research, a population of mononuclear leukocytes was isolated from the peripheral blood of healthy donors by gradient centrifugation. The cell suspension was placed in a round-bottomed plates with preliminarily added polyamines at concentrations of 5, 25, 50, 75, and 100 mmol/L. Wells not containing polyamines were used as a control. After incubation for 72 h at 37 °C and 5% CO2, the supernatants were harvested and used to determine the concentration of IL-10. We used a kit for determining the concentration of IL-10 using the enzyme immunoassay method (Russia). Statistical analysis was performed using the Statistica 6.0 software package. In the case of a distribution close to normal, Student’s t-test was used; in the rest, the Mann–Whitney test was used to assess the significance of differences. Studies have shown that leukocytes in the presence of concanavalin A produce IL-10 at a concentration of 17.13±6.08 pg/mL. It has been established that under the influence of polyamines of bacterial origin, the production of IL-10 is enhanced only if putrescine and cadaverine are at concentrations of 50 mmol/L and higher. At low concentrations of polyamines, no significant increase in IL-10 production was detected. Since IL-10 is an anti- inflammatory cytokine, for which the analgesic effect is also known, it should be expected that with an increase in its concentration in the focus of invasion of opportunistic bacteria, the inflammatory process will develop latently, when the symptoms are mild. In general, it can be expected that polyamine-producing bacteria will contribute to the maintenance of few symptomatic inflammation.
{"title":"Influence of microbial polyamines on the IL-10 production by peripheral blood leukocytes of healthy donors","authors":"А. Р. Godovalov, I. A. Morozov","doi":"10.15789/1563-0625-iom-2842","DOIUrl":"https://doi.org/10.15789/1563-0625-iom-2842","url":null,"abstract":"As is known, bacterial polyamines, which include cadaverine and putrescine, are capable of influencing the activity of immunocompetent cells in many ways. In particular, this situation is observed in long-term inflammatory diseases, especially with intensive reproduction of microorganisms capable of producing polyamines. It is of interest to study the production of one of the main anti-inflammatory cytokines, IL-10, under the influence of bacterial polyamines. For research, a population of mononuclear leukocytes was isolated from the peripheral blood of healthy donors by gradient centrifugation. The cell suspension was placed in a round-bottomed plates with preliminarily added polyamines at concentrations of 5, 25, 50, 75, and 100 mmol/L. Wells not containing polyamines were used as a control. After incubation for 72 h at 37 °C and 5% CO2, the supernatants were harvested and used to determine the concentration of IL-10. We used a kit for determining the concentration of IL-10 using the enzyme immunoassay method (Russia). Statistical analysis was performed using the Statistica 6.0 software package. In the case of a distribution close to normal, Student’s t-test was used; in the rest, the Mann–Whitney test was used to assess the significance of differences. Studies have shown that leukocytes in the presence of concanavalin A produce IL-10 at a concentration of 17.13±6.08 pg/mL. It has been established that under the influence of polyamines of bacterial origin, the production of IL-10 is enhanced only if putrescine and cadaverine are at concentrations of 50 mmol/L and higher. At low concentrations of polyamines, no significant increase in IL-10 production was detected. Since IL-10 is an anti- inflammatory cytokine, for which the analgesic effect is also known, it should be expected that with an increase in its concentration in the focus of invasion of opportunistic bacteria, the inflammatory process will develop latently, when the symptoms are mild. In general, it can be expected that polyamine-producing bacteria will contribute to the maintenance of few symptomatic inflammation.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84640876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-poi-2702
A. Aleksandrov, L. Shilova, V. Aleksandrov, M. Levkina, O. Paramonova, N. Aleksandrova, I. Zborovskaya
The study aimed to evaluate the association between cyclic citrullinated peptide antibody seropositivity and chronic Helicobacter pylori (H. pylori) infection in patients with rheumatoid arthritis (RA). We examined 92 women with moderate RA activity. Serum antibodies to cyclic citrullinated peptide (antiCCP), antibodies to H. pylori (anti-H. pylori-IgG), and total antibodies to H. pylori CagA antigen (antiCagA) were determined by enzyme immunoassay; the presence of anti-CagA-IgG positivity was confirmed by immunoblot. 68.5% of RA patients were positive for anti-H. pylori-IgG, and 44.4% of patients in this group were positive for anti-CagA-IgG. All the study participants were divided into three groups: I – H. pylori seronegative (H. pylori- ); II – H. pylori positive, CagA negative (H. pylori+/CagA- ); III – H. pylori positive and CagA positive (CagA+). The anti-CCP values in RA patients with CagA+ (group III) were significantly higher not only in comparison with patients seronegative for H. pylori (p < 0.001), but also in comparison with patients from group II (H. pylori+/CagA- ) (p = 0.041). A study of the influence of the RA activity, the presence of RF and H. pylori on anti-CCP content demonstrated a small proportion of anti-CCP variability (R2 = 0.09), with a high contribution of H. pylori (beta = 0.25). The addition of the CagA(+) index (beta = 0.503) to the presented model allowed us to describe the variability of anti-CCP in almost 30% of cases (R2 = 0.29). In the group of RA patients with anti-CCP values exceeding the established threshold value of 20 U/mL (normal index), there was an increase in the proportion of patients infected with H. pylori (p < 0.001), but not the proportion of CagA-positive patients (p = 0.06). When the threshold level was increased to 60 U/mL (three times the upper limit of normal) in patients with significantly high anti-CCP, the association with positivity for CagA became significant (p = 0.005). CagA is highly immunogenic and is capable of inducing an inflammatory response in the host that goes beyond the effect of H. pylori itself. Additional experimental studies are needed to investigate possible clinical and laboratory associations that may influence the treatment tactics of CagA+ patients with RA who are seropositive for anti-citrullinated antibodies, as well as to evaluate the possible effects of therapeutic intervention aimed at the eradication of H. pylori in this group.
{"title":"Peculiarities of immunological manifestations in patients with rheumatoid arthritis in the presence of chronic infection with Helicobacter pylori variant encoding cytotoxin-associated gene A","authors":"A. Aleksandrov, L. Shilova, V. Aleksandrov, M. Levkina, O. Paramonova, N. Aleksandrova, I. Zborovskaya","doi":"10.15789/1563-0625-poi-2702","DOIUrl":"https://doi.org/10.15789/1563-0625-poi-2702","url":null,"abstract":"The study aimed to evaluate the association between cyclic citrullinated peptide antibody seropositivity and chronic Helicobacter pylori (H. pylori) infection in patients with rheumatoid arthritis (RA). We examined 92 women with moderate RA activity. Serum antibodies to cyclic citrullinated peptide (antiCCP), antibodies to H. pylori (anti-H. pylori-IgG), and total antibodies to H. pylori CagA antigen (antiCagA) were determined by enzyme immunoassay; the presence of anti-CagA-IgG positivity was confirmed by immunoblot. 68.5% of RA patients were positive for anti-H. pylori-IgG, and 44.4% of patients in this group were positive for anti-CagA-IgG. All the study participants were divided into three groups: I – H. pylori seronegative (H. pylori- ); II – H. pylori positive, CagA negative (H. pylori+/CagA- ); III – H. pylori positive and CagA positive (CagA+). The anti-CCP values in RA patients with CagA+ (group III) were significantly higher not only in comparison with patients seronegative for H. pylori (p < 0.001), but also in comparison with patients from group II (H. pylori+/CagA- ) (p = 0.041). A study of the influence of the RA activity, the presence of RF and H. pylori on anti-CCP content demonstrated a small proportion of anti-CCP variability (R2 = 0.09), with a high contribution of H. pylori (beta = 0.25). The addition of the CagA(+) index (beta = 0.503) to the presented model allowed us to describe the variability of anti-CCP in almost 30% of cases (R2 = 0.29). In the group of RA patients with anti-CCP values exceeding the established threshold value of 20 U/mL (normal index), there was an increase in the proportion of patients infected with H. pylori (p < 0.001), but not the proportion of CagA-positive patients (p = 0.06). When the threshold level was increased to 60 U/mL (three times the upper limit of normal) in patients with significantly high anti-CCP, the association with positivity for CagA became significant (p = 0.005). CagA is highly immunogenic and is capable of inducing an inflammatory response in the host that goes beyond the effect of H. pylori itself. Additional experimental studies are needed to investigate possible clinical and laboratory associations that may influence the treatment tactics of CagA+ patients with RA who are seropositive for anti-citrullinated antibodies, as well as to evaluate the possible effects of therapeutic intervention aimed at the eradication of H. pylori in this group.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81748571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-aof-2809
K. T. Muminova, Z. Khodzhaeva, E. Yarotskaya, M. M. Ziganshina
Systemic inflammation alongside endothelial dysfunction is considered to play a crucial role in PE pathogenesis. Endothelial dysfunction can be assessed by endothelial glycocalyx (eGC) damage. eGC is a superficial layer of cells associated with endothelial membrane that provides all endothelial cells functions. Its damage can be evaluated by the levels of its circulating components in blood. Patients with PE generally receive methyldopa (Dopegyt) solely or in combination with nifedipine (Cordaflex), and there is no understanding of their effect on proinflammatory state of blood vessels. Our study aimed to assess levels of IL-6, IL-18, TNFα, galektin-3 and homocysteine as well as levels of syndecan-1, eCG structural component, representing system inflammatory response and endothelial dysfunction development in blood of women with early- and late-onset PE receiving different antihypertensive treatment strategies. Eighty-two patients were enrolled into this interventional longitudinal pilot study. The comparison group included 15 patients before 34 gestational weeks and 15 patients after 34 weeks. Study subgroup 1 included 12 patients with early- onset PE receiving Dopegyt solely and 16 patients with early-onset PE receiving Dopegyt together with Cordaflex. Study subgroup 2 included 12 patients with late-onset PE receiving Dopegyt solely and 12 patients with late-onset PE receiving combined therapy. As for early-onset PE, only IL-6 demonstrated statistically significant differences in patients receiving both treatment strategies compared to control. Proinflammatory state was more profound in late-onset PE. IL-6 levels were significantly increased in late-onset PE treated with Dopegyt. IL-6 and TNFa levels were significantly higher in late-onset PE patients treated with Dopegyt + Cordaflex compared to control. Syndecan-1 levels were statistically significantly higher in patients with early-onset PE treated with Dopegyt solely. There were no statistically significant differences between the groups despite elevated mean values of syndecan-1 in late-onset PE. Galectin-3 and homocysteine levels did not differ significantly between the groups, representing lack of pronounced inflammatory response and endothelial dysfunction.
{"title":"Analysis of factors associated with sterile inflammation in women with pe receiving different antihypertensive treatment strategies","authors":"K. T. Muminova, Z. Khodzhaeva, E. Yarotskaya, M. M. Ziganshina","doi":"10.15789/1563-0625-aof-2809","DOIUrl":"https://doi.org/10.15789/1563-0625-aof-2809","url":null,"abstract":"Systemic inflammation alongside endothelial dysfunction is considered to play a crucial role in PE pathogenesis. Endothelial dysfunction can be assessed by endothelial glycocalyx (eGC) damage. eGC is a superficial layer of cells associated with endothelial membrane that provides all endothelial cells functions. Its damage can be evaluated by the levels of its circulating components in blood. Patients with PE generally receive methyldopa (Dopegyt) solely or in combination with nifedipine (Cordaflex), and there is no understanding of their effect on proinflammatory state of blood vessels. Our study aimed to assess levels of IL-6, IL-18, TNFα, galektin-3 and homocysteine as well as levels of syndecan-1, eCG structural component, representing system inflammatory response and endothelial dysfunction development in blood of women with early- and late-onset PE receiving different antihypertensive treatment strategies. Eighty-two patients were enrolled into this interventional longitudinal pilot study. The comparison group included 15 patients before 34 gestational weeks and 15 patients after 34 weeks. Study subgroup 1 included 12 patients with early- onset PE receiving Dopegyt solely and 16 patients with early-onset PE receiving Dopegyt together with Cordaflex. Study subgroup 2 included 12 patients with late-onset PE receiving Dopegyt solely and 12 patients with late-onset PE receiving combined therapy. As for early-onset PE, only IL-6 demonstrated statistically significant differences in patients receiving both treatment strategies compared to control. Proinflammatory state was more profound in late-onset PE. IL-6 levels were significantly increased in late-onset PE treated with Dopegyt. IL-6 and TNFa levels were significantly higher in late-onset PE patients treated with Dopegyt + Cordaflex compared to control. Syndecan-1 levels were statistically significantly higher in patients with early-onset PE treated with Dopegyt solely. There were no statistically significant differences between the groups despite elevated mean values of syndecan-1 in late-onset PE. Galectin-3 and homocysteine levels did not differ significantly between the groups, representing lack of pronounced inflammatory response and endothelial dysfunction.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80076994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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