Mingxing Yang, Guowei Xu, Jingyan Zhang, Zhiting Guo, Chao Liang, Yajun Li, Lei Wang, Yuxia Zhou, Yi Ru, Jianxi Li, Xuezhi Wang, Yan Sun
Feline interferon omega (IFN-ω) has been proven to have high antiviral activity; however, its in-depth antiviral effects remain unknown. Extracellular vesicles (EVs) have been demonstrated to participate in the regulation of the immune response pathway for the body through various active substances, especially through the microRNA (miRNA) carried by them. In this study, we isolated EVs from feline peripheral blood by differential centrifugation, and further found that the content of IFN-ω in EVs increased continuously within 24 h after IFN-ω treatment, and a large number of miRNAs were significantly downregulated in EVs within 12 h after IFN-ω treatment. These significantly differentially expressed miRNAs were important for regulating changes in antiviral cytokines. This study reveals for the first time the correlation between EVs-mediated miRNA in feline peripheral blood and IFN-ω on antiviral immune response, which may provide strong data support for the development of novel antiviral nanomedicine and the research of the antiviral effects of IFN-ω.
{"title":"Correlation Between MicroRNA by Extracellular Vesicle Mediated and Antiviral Effects of Interferon Omega in Feline Peripheral Blood.","authors":"Mingxing Yang, Guowei Xu, Jingyan Zhang, Zhiting Guo, Chao Liang, Yajun Li, Lei Wang, Yuxia Zhou, Yi Ru, Jianxi Li, Xuezhi Wang, Yan Sun","doi":"10.1089/jir.2023.0174","DOIUrl":"10.1089/jir.2023.0174","url":null,"abstract":"<p><p>Feline interferon omega (IFN-ω) has been proven to have high antiviral activity; however, its in-depth antiviral effects remain unknown. Extracellular vesicles (EVs) have been demonstrated to participate in the regulation of the immune response pathway for the body through various active substances, especially through the microRNA (miRNA) carried by them. In this study, we isolated EVs from feline peripheral blood by differential centrifugation, and further found that the content of IFN-ω in EVs increased continuously within 24 h after IFN-ω treatment, and a large number of miRNAs were significantly downregulated in EVs within 12 h after IFN-ω treatment. These significantly differentially expressed miRNAs were important for regulating changes in antiviral cytokines. This study reveals for the first time the correlation between EVs-mediated miRNA in feline peripheral blood and IFN-ω on antiviral immune response, which may provide strong data support for the development of novel antiviral nanomedicine and the research of the antiviral effects of IFN-ω.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"44 3","pages":"124-134"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-02-20DOI: 10.1089/jir.2023.0157
Emmanuel Kontomanolis, Christina Tsigalou, Achilleas Mitrakas, Anastasia G Gkegka, Eleni Efraimidou, Dimitrios Karamanidis, Konstantinos Nikoletos, Tsikouras Panagiotis, Nikolaos Nikoletos, Alexandra Giatromanolaki, Michael I Koukourakis
Studying the levels of cytokines in the plasma of patients could be valuable in guiding immunotherapy policies. We assessed the plasma levels of 4 major cytokines [interferon (IFN)-β, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β)] collected from 19 patients with ductal breast cancer (BCa), before surgery (BS) and 5 days after surgery (AS). The ratio AS/BS was also calculated and correlated with histopathological variables and tumor-infiltrating lymphocyte (TIL) density. The IFN-β and TNF-α levels were significantly higher in BCa patients, BS and AS, than healthy controls (P < 0.02). High IL-2 levels BS were linked with node involvement (P = 0.02), and marginally with HER2 expression (P = 0.08), while high TNF-α levels were linked with high PgR expression (P = 0.02). Increasing IFN-β, IL-2, and TNF-α levels were noted AS, which was more evident in patients with larger tumors. The TGF-β levels were significantly lower in BCa patients (P < 0.007). Linear regression analysis showed a direct association of IFN-β levels AS (P = 0.02, r = 0.52) and of TNF-α AS/BS-ratio (P = 0.001, r = 0.72) with TIL-density. It is suggested that although effector immune response is evident in the majority of early stage BCa patients, removal of the primary tumor further unblocks such responses.
{"title":"Cytokine Plasma Levels in Breast Cancer Patients, Before and After Surgery.","authors":"Emmanuel Kontomanolis, Christina Tsigalou, Achilleas Mitrakas, Anastasia G Gkegka, Eleni Efraimidou, Dimitrios Karamanidis, Konstantinos Nikoletos, Tsikouras Panagiotis, Nikolaos Nikoletos, Alexandra Giatromanolaki, Michael I Koukourakis","doi":"10.1089/jir.2023.0157","DOIUrl":"10.1089/jir.2023.0157","url":null,"abstract":"<p><p>Studying the levels of cytokines in the plasma of patients could be valuable in guiding immunotherapy policies. We assessed the plasma levels of 4 major cytokines [interferon (IFN)-β, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β)] collected from 19 patients with ductal breast cancer (BCa), before surgery (BS) and 5 days after surgery (AS). The ratio AS/BS was also calculated and correlated with histopathological variables and tumor-infiltrating lymphocyte (TIL) density. The IFN-β and TNF-α levels were significantly higher in BCa patients, BS and AS, than healthy controls (<i>P</i> < 0.02). High IL-2 levels BS were linked with node involvement (<i>P</i> = 0.02), and marginally with HER2 expression (<i>P</i> = 0.08), while high TNF-α levels were linked with high PgR expression (<i>P</i> = 0.02). Increasing IFN-β, IL-2, and TNF-α levels were noted AS, which was more evident in patients with larger tumors. The TGF-β levels were significantly lower in BCa patients (<i>P</i> < 0.007). Linear regression analysis showed a direct association of IFN-β levels AS (<i>P</i> = 0.02, <i>r</i> = 0.52) and of TNF-α AS/BS-ratio (<i>P</i> = 0.001, <i>r</i> = 0.72) with TIL-density. It is suggested that although effector immune response is evident in the majority of early stage BCa patients, removal of the primary tumor further unblocks such responses.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"135-142"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-02-01DOI: 10.1089/jir.2023.0162
Reham Mohammed Dawood, Ghada Maher Salum, Mai Abd El-Meguid, Basma El-Sayed Fotouh
Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease. Many hepatic abnormalities are associated with NAFLD such as nonalcoholic steatohepatitis, progressive fibrosis, cirrhosis, and liver failure. Moreover, the pathogenesis of NAFLD has numerous etiologies and can be explained due to the existence of several of stimulus that act simultaneously on genetically susceptible patients. These stimuli include obesity, diabetes, and insulin resistance. In addition, identifying the role of gut microbiota on NAFLD progression has been illustrated. In this review, we clarified the several factors that lead to the development of NAFLD and identify those who are most at risk of developing liver end-stage disease. Highlighting the noninvasive diagnostic NAFLD markers could be helpful in the disease prevention and treatment approaches.
{"title":"Molecular Insights of Nonalcoholic Fatty Liver Disease Pathogenesis.","authors":"Reham Mohammed Dawood, Ghada Maher Salum, Mai Abd El-Meguid, Basma El-Sayed Fotouh","doi":"10.1089/jir.2023.0162","DOIUrl":"10.1089/jir.2023.0162","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease. Many hepatic abnormalities are associated with NAFLD such as nonalcoholic steatohepatitis, progressive fibrosis, cirrhosis, and liver failure. Moreover, the pathogenesis of NAFLD has numerous etiologies and can be explained due to the existence of several of stimulus that act simultaneously on genetically susceptible patients. These stimuli include obesity, diabetes, and insulin resistance. In addition, identifying the role of gut microbiota on NAFLD progression has been illustrated. In this review, we clarified the several factors that lead to the development of NAFLD and identify those who are most at risk of developing liver end-stage disease. Highlighting the noninvasive diagnostic NAFLD markers could be helpful in the disease prevention and treatment approaches.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"111-123"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-28DOI: 10.1089/jir.2023.0101
Richard Salama-Frisbie, Cinthia A Molina-Flores, Arguiñe I Urraza-Robledo, María E Gutiérrez-Pérez, Alberto A Miranda-Pérez, Alhi A Gutiérrez-Salas, Jorge Haro-Santa Cruz, Francisco C López-Márquez
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.
{"title":"Association of Polymorphisms of the <i>IL-17A</i> and <i>IL-17F</i> Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.","authors":"Richard Salama-Frisbie, Cinthia A Molina-Flores, Arguiñe I Urraza-Robledo, María E Gutiérrez-Pérez, Alberto A Miranda-Pérez, Alhi A Gutiérrez-Salas, Jorge Haro-Santa Cruz, Francisco C López-Márquez","doi":"10.1089/jir.2023.0101","DOIUrl":"10.1089/jir.2023.0101","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the <i>IL-17A</i> rs2275913 and <i>IL-17F</i> rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan<sup>®</sup> probe. There was no association between the AA genotype and A allele of IL-17A variant or the <i>IL-17F</i> C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between <i>IL-17A</i> rs2275913 AA genotype and hypertension, as well as with the presence of obesity (<i>P</i> = 0.003, OR 23, 95% CI: 2.97-178.092 and <i>P</i> = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 <i>IL-17A</i> polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"60-67"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-01-29DOI: 10.1089/jir.2023.0207
Mary McCabe
{"title":"Cytokines 2023: 11th Annual Meeting of the International Cytokine and Interferon Society.","authors":"Mary McCabe","doi":"10.1089/jir.2023.0207","DOIUrl":"10.1089/jir.2023.0207","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"94-98"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-01-17DOI: 10.1089/jir.2023.0103
Iwona Zaporowska-Stachowiak, Michał Springer, Katarzyna Stachowiak, Mary Oduah, Maciej Sopata, Katarzyna Wieczorowska-Tobis, Wiesław Bryl
Nine soluble ligands [interleukin-6 (IL-6), interleukin-11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine, interleukin-27 (IL-27), and interleukin-31] share the ubiquitously expressed transmembrane protein-glycoprotein-130 beta-subunit (gp130) and thus form IL-6 family cytokines. Proteins that may be important for cancerogenesis, CT-1, IL-11, IL-27, LIF, OSM, and CNTF, belong to the superfamily of IL-6. Cytokines such as IL-6, IL-11, and IL-27 are better investigated in comparison with other members of the same family of cytokines, eg, CT-1. Gp130 is one of the main receptors through which these cytokines exert their effects. The clinical implication of understanding the pathways of these cytokines in oncology is that targeted therapy to inhibit or potentiate cytokine activity may lead to remission in some cases.
{"title":"Interleukin-6 Family of Cytokines in Cancers.","authors":"Iwona Zaporowska-Stachowiak, Michał Springer, Katarzyna Stachowiak, Mary Oduah, Maciej Sopata, Katarzyna Wieczorowska-Tobis, Wiesław Bryl","doi":"10.1089/jir.2023.0103","DOIUrl":"10.1089/jir.2023.0103","url":null,"abstract":"<p><p>Nine soluble ligands [interleukin-6 (IL-6), interleukin-11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine, interleukin-27 (IL-27), and interleukin-31] share the ubiquitously expressed transmembrane protein-glycoprotein-130 beta-subunit (gp130) and thus form IL-6 family cytokines. Proteins that may be important for cancerogenesis, CT-1, IL-11, IL-27, LIF, OSM, and CNTF, belong to the superfamily of IL-6. Cytokines such as IL-6, IL-11, and IL-27 are better investigated in comparison with other members of the same family of cytokines, eg, CT-1. Gp130 is one of the main receptors through which these cytokines exert their effects. The clinical implication of understanding the pathways of these cytokines in oncology is that targeted therapy to inhibit or potentiate cytokine activity may lead to remission in some cases.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"45-59"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-28DOI: 10.1089/jir.2023.0132
Liangwei Chen, Dihao Pan, Yiran Zhang, Enfan Zhang, Liang Ma
Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing in vivo.
{"title":"C-C Motif Chemokine 2 Regulates Macrophage Polarization and Contributes to Myocardial Infarction Healing.","authors":"Liangwei Chen, Dihao Pan, Yiran Zhang, Enfan Zhang, Liang Ma","doi":"10.1089/jir.2023.0132","DOIUrl":"10.1089/jir.2023.0132","url":null,"abstract":"<p><p>Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing <i>in vivo</i>.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"68-79"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leptospirosis has a wide spectrum of clinical manifestations ranging from mild to severe disease. The cytokine response is considered one of the key drivers for this varying manifestation. The different cytokine response observed in patients with leptospirosis could be due to the variation of infecting serovars. Since the rfb locus codes for the lipopolysaccharide synthesis of the bacterial cell wall, which also determines the serovar, this locus may play a role in driving a specific cytokine response in the host. We investigated 12 commonly used cytokine profiles in serum samples of culture, microscopic agglutination test (MAT), or polymerase chain reaction (PCR)-positive patients with leptospirosis. The sequences of the rfb locus in culture-positive samples were generated from whole genome sequencing and serovar status was drawn from original data published. Isolated cultures were subjected to whole genome sequencing using the PacBio RS II system, and the resulting data were used to determine the species. The recovered genomic data were annotated with the Rapid Annotation using Subsystem Technology (RAST) subsystem, and the rfb locus was extracted. The cytokine analysis was carried out using the Qiagen human ELISA kit. Eighteen samples were found to be positive by culture, while the other 7 samples were positive by PCR or MAT. Infections from Leptospira interrogans serovar Autumnalis (5), Pyrogens (3), Icterohaemorrhagiae (1) Leptospira borgpetersenii (all 7 samples clustered in same clonal group with serovar status not determined), Leptospira weilii (1 with serovar status not determined), and Leptospira kirschneri serovar Grippotyphosa (1) were included in the analysis. Three patients [infected with Leptospira interrogansserovar Autumnalis (2) and Pyrogens (1)] and 2 MAT-positive patients (highest titer against serovar Bratislava of L.interrognas) were reported to have severe clinical manifestations, while the rest had mild to moderate symptoms. Although the serum cytokine concentration of patients with severe clinical manifestation was comparatively higher, a statistically significant difference was observed only for interleukin (IL)-1β (P < 0.05). IL-10/tumor necrosis factor-alpha (TNF-α) ratio was high in patients with severe complications. In general, patients infected with L. interrogans showed higher concentration of cytokines compared to L. borgpetersenii.
{"title":"Levels of Cytokines in Leptospirosis Patients with Different Serovars and <i>rfb</i> Locus.","authors":"Indika Senavirathna, Dinesha Jayasundara, Janith Warnasekara, Chamila Kappagoda, Suneth Agampodi","doi":"10.1089/jir.2023.0091","DOIUrl":"10.1089/jir.2023.0091","url":null,"abstract":"<p><p>Leptospirosis has a wide spectrum of clinical manifestations ranging from mild to severe disease. The cytokine response is considered one of the key drivers for this varying manifestation. The different cytokine response observed in patients with leptospirosis could be due to the variation of infecting serovars. Since the <i>rfb</i> locus codes for the lipopolysaccharide synthesis of the bacterial cell wall, which also determines the serovar, this locus may play a role in driving a specific cytokine response in the host. We investigated 12 commonly used cytokine profiles in serum samples of culture, microscopic agglutination test (MAT), or polymerase chain reaction (PCR)-positive patients with leptospirosis. The sequences of the <i>rfb</i> locus in culture-positive samples were generated from whole genome sequencing and serovar status was drawn from original data published. Isolated cultures were subjected to whole genome sequencing using the PacBio RS II system, and the resulting data were used to determine the species. The recovered genomic data were annotated with the Rapid Annotation using Subsystem Technology (RAST) subsystem, and the rfb locus was extracted. The cytokine analysis was carried out using the Qiagen human ELISA kit. Eighteen samples were found to be positive by culture, while the other 7 samples were positive by PCR or MAT. Infections from <i>Leptospira interrogans serovar Autumnalis (5), Pyrogens (3), Icterohaemorrhagiae (1) Leptospira borgpetersenii</i> (all 7 samples clustered in same clonal group with serovar status not determined), <i>Leptospira weilii</i> (1 with serovar status not determined), and <i>Leptospira kirschneri</i> serovar Grippotyphosa (1) were included in the analysis. Three patients [infected with <i>Leptospira interrogans</i>serovar Autumnalis (2) and Pyrogens (1)] and 2 MAT-positive patients (highest titer against serovar Bratislava of <i>L.interrognas</i>) were reported to have severe clinical manifestations, while the rest had mild to moderate symptoms. Although the serum cytokine concentration of patients with severe clinical manifestation was comparatively higher, a statistically significant difference was observed only for interleukin (IL)-1β (<i>P</i> < 0.05). IL-10/tumor necrosis factor-alpha (TNF-α) ratio was high in patients with severe complications. In general, patients infected with <i>L. interrogans</i> showed higher concentration of cytokines compared to <i>L. borgpetersenii</i>.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"44 2","pages":"80-93"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-11-29DOI: 10.1089/jir.2023.0090
Ali Azizi, Nasrin Mansouri, Mitra Tarlan, Masoud Sadeghi
Interleukin-6 (IL-6) has obviously tumor-promoting and tumor-inhibitory effects and can induce an epithelial-mesenchymal transition phenotype in human breast cancer (BC) cells and implicate its potential to promote BC metastasis. Herein, we aimed to evaluate the association of IL-6 variants (rs1800795, rs1800796, rs1554606, rs1800797, rs2069840, rs12700386, and rs2069861) with the susceptibility to BC. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library were searched until December 19, 2022, without any restrictions. The quality assessment of each study was performed based on the Newcastle-Ottawa Scale tool. The Review Manager 5.3 software presented the effect sizes including odds ratio (OR) along with a 95% confidence interval (CI). Both publication bias and sensitivity analyses were carried out by the Comprehensive Meta-Analysis version 2.0 software. A total of 2,508 records were identified among databases and at last, 27 articles were entered into the meta-analysis. Seven polymorphisms of IL-6 were entered into the analyses. Just rs1800797 polymorphism in the dominant model (OR = 1.51; 95% CI = 1.15-2.00; P = 0.003) and rs2069840 polymorphism in heterozygous (OR = 0.89; 95% CI = 0.81-0.97; P = 0.008) and dominant (OR = 0.91; 95% CI = 0.84-0.99; P = 0.02) models had a significant association with the BC risk. In conclusion, among 7 polymorphisms and despite a few included cases, the present meta-analysis recommended that the AA+GA genotype of rs1800797 polymorphism had a significantly elevated risk and the GC and the CC+GC genotypes of rs2069840 polymorphism had a protective role in the BC patients.
白细胞介素-6 (IL-6)具有明显的促瘤和抑瘤作用,可诱导人乳腺癌细胞上皮-间质转化表型,并可能促进乳腺癌转移。在此,我们旨在评估IL-6变异(rs1800795、rs1800796、rs1554606、rs1800797、rs2069840、rs12700386和rs2069861)与BC易感性的关系。检索PubMed/Medline、Web of Science、Scopus、Cochrane Library等数据库至2022年12月19日,无任何限制。每个研究的质量评估是基于纽卡斯尔-渥太华量表工具进行的。Review Manager 5.3软件显示了包括优势比(OR)和95%置信区间(CI)在内的效应大小。发表偏倚和敏感性分析均采用综合meta分析2.0版软件进行。在数据库中共识别2508条记录,最终有27篇文章被纳入meta分析。IL-6的7个多态性被纳入分析。优势模型只有rs1800797多态性(OR = 1.51;95% ci = 1.15-2.00;P = 0.003),杂合子rs2069840多态性(OR = 0.89;95% ci = 0.81-0.97;P = 0.008)和显性(OR = 0.91;95% ci = 0.84-0.99;P = 0.02)模型与BC风险显著相关。综上所述,在7个多态性中,除了少数纳入病例外,本meta分析提示rs1800797多态性的AA+GA基因型在BC患者中具有显著升高的风险,rs2069840多态性的GC和CC+GC基因型在BC患者中具有保护作用。
{"title":"Analysis of <i>Interleukin-6</i> Gene Variants (<i>rs1800795</i>, <i>rs1800796</i>, <i>rs1554606</i>, <i>rs1800797</i>, <i>rs2069840</i>, <i>rs12700386</i>, and <i>rs2069861</i>) as Prognostic Markers in Breast Cancer: A Systematic Review, Meta-Analysis, and Network Analysis.","authors":"Ali Azizi, Nasrin Mansouri, Mitra Tarlan, Masoud Sadeghi","doi":"10.1089/jir.2023.0090","DOIUrl":"10.1089/jir.2023.0090","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) has obviously tumor-promoting and tumor-inhibitory effects and can induce an epithelial-mesenchymal transition phenotype in human breast cancer (BC) cells and implicate its potential to promote BC metastasis. Herein, we aimed to evaluate the association of <i>IL-6</i> variants (<i>rs1800795</i>, <i>rs1800796</i>, <i>rs1554606</i>, <i>rs1800797</i>, <i>rs2069840</i>, <i>rs12700386</i>, and <i>rs2069861</i>) with the susceptibility to BC. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library were searched until December 19, 2022, without any restrictions. The quality assessment of each study was performed based on the Newcastle-Ottawa Scale tool. The Review Manager 5.3 software presented the effect sizes including odds ratio (OR) along with a 95% confidence interval (CI). Both publication bias and sensitivity analyses were carried out by the Comprehensive Meta-Analysis version 2.0 software. A total of 2,508 records were identified among databases and at last, 27 articles were entered into the meta-analysis. Seven polymorphisms of IL-6 were entered into the analyses. Just <i>rs1800797</i> polymorphism in the dominant model (OR = 1.51; 95% CI = 1.15-2.00; <i>P</i> = 0.003) and <i>rs2069840</i> polymorphism in heterozygous (OR = 0.89; 95% CI = 0.81-0.97; <i>P</i> = 0.008) and dominant (OR = 0.91; 95% CI = 0.84-0.99; <i>P</i> = 0.02) models had a significant association with the BC risk. In conclusion, among 7 polymorphisms and despite a few included cases, the present meta-analysis recommended that the AA+GA genotype of <i>rs1800797</i> polymorphism had a significantly elevated risk and the GC and the CC+GC genotypes of <i>rs2069840</i> polymorphism had a protective role in the BC patients.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"3-15"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-12-29DOI: 10.1089/jir.2023.29058.editorial
Yan Ma
{"title":"The \"Yin-Yang\" Activities of Tumor-Induced Inflammatory Cytokines for Cancer Immunotherapy, Detection, and Prognosis.","authors":"Yan Ma","doi":"10.1089/jir.2023.29058.editorial","DOIUrl":"10.1089/jir.2023.29058.editorial","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"1-2"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}