European cytokine network最新文献

The aim of the present study was to evaluate the diagnostic significance of the dynamics of cytokines and growth factors during pregnancy with and without preeclampsia. The study included 168 pregnant women at risk of hypertensive disorders. The levels of biomarkers of all pregnant women were studied at 12-16 weeks, 28-30 weeks and 36-38 weeks. These included cytokines (tumour necrosis factor-α, interferon-, γinterleukin-4) and growth factors (placental growth factor, vascular endothelial growth factor). All pregnant women were divided into two groups: 124 patients with preeclampsia and 44 without preeclampsia (control group). In patients with preeclampsia, an increase in the level of tumour necrosis factorα- was observed, compared with the control group: a 6.1-fold increase at 12-16 weeks and a 5.9-fold increase at 36-38 weeks. The level of interferon-γ was also increased, by 44.3% in the first trimester of pregnancy and by 46.8% at 28-30 weeks, compared to the control group. The level of interleukin-4 did not significantly differ between the studied groups. The level of placental growth factor was reduced in pregnant women with preeclampsia at all stages of gestation, and at 28-30 weeks was reduced by 67.9% compared to the control group. The level of vascular endothelial growth factor was also reduced, by 75%, compared with the control group. An increase in the level of pro-inflammatory cytokines and decrease in growth factors may therefore be considered as potential predictors of the development of preeclampsia, and evaluation of these factors may be advocated in pregnant women with risk factors of preeclampsia.

The blood-brain barrier (BBB) consists of a unique system of brain microvascular endothelial cells, capillary basement membranes, and terminal branches ("end-feet") of astrocytes. The BBB's primary function is to protect the central nervous system from potentially harmful or toxic substances in the bloodstream by selectively controlling the entry of cells and molecules, including nutrients and immune system components. During neuroinflammation, the BBB loses its integrity, resulting in increased permeability, mostly due to the activity of inflammatory cytokines. However, the pathomechanism of structural and functional changes in the BBB caused by individual cytokines is poorly understood. This review summarizes the current state of knowledge on this topic, which is important from both the pathophysiological and clinical-therapeutic point of view. The structure and function of each of the components of the BBB are discussed with particular attention to phenotypic differences between brain microvascular endothelial cells and the vascular endothelium at other locations of the circulatory system. The protein composition of the inter-endothelial tight junctions in the context of regulating BBB permeability is presented, as is the role of the pericyte-BMEC interaction in the exchange of metabolites, ions, and nucleic acids. Finally, the documented actions of proinflammatory cytokines within the BBB are summarized.

Pancreatic cancer (PC) is one of the leading causes of cancer deaths, associated with a high risk of metastasis and mortality. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is highly expressed in multiple types of tumour tissues and may be associated with the growth of PC cells. In this study, we aimed to assess the role and possible mechanisms of MALAT1 in PC progression. Expression of MALAT1 was studied by quantitative real-time polymerase chain reaction (qRT-PCR) in PC tissues. The dual-luciferase assay was performed to validate binding between MALAT1 and miR-141-5p in HEK293 cells. Western blot analysis was performed to examine the expression of transforming growth factor beta (TGF-β) and its receptors, TGFBR1 and TGFBR2. Invasiveness and migration of cultured PANC-1 cells were studied using transwell invasion and migration assays, respectively. A high level of miR-141-5p and low level of MALAT1 were detected in PC tissues, and the level of MALAT1 was shown to significantly correlate with tumour growth and metastasis. In HEK293 cells, miR-141-5p overexpression inhibited the expression of TGFBR1 and TGFBR2, and this inhibition was reversed by overexpression of MALAT1. In PANC-1 cells, MALAT1 was shown to act as a competing endogenous RNA, as the direct target of miR-141-5p. Furthermore, in PANC-1 cells, miR-141-5p overexpression suppressed TGF-induced epithelial-mesenchymal transition (EMT), cell migration, and cell invasion through direct binding to the 3'UTR of TGFBR1 and TGFBR2. Our results indicate that, in PC cells, miR-141-5p suppresses TGFBR1 and TGFBR2 expression and further inhibits TGF-β-induced EMT, cell migration, and cell invasion, which are reversed by overexpression of MALAT1, demonstrating that MALAT1 and miR-141-5p may be important regulators in the initiation and metastasis of PC.

Primary Sjögren syndrome (pSS) is a systemic autoimmune disorder that affects various systems in the body, resulting in symptoms such as dry eyes and mouth, pain, and fatigue. Inflammation plays a critical role in pSS and its associated complications, with chronic inflammation being a common occurrence in patients with pSS. This review of the literature highlights inflammatory markers that could serve as indicators to predict disease progression in pSS. Laboratory markers are frequently and significantly increased in pSS patients, including erythrocyte sedimentation rate, C-reactive protein, complement proteins, S100 proteins, cytokines (IFNs, CD40 ligand, soluble CD25, rheumatoid factors, interleukins, and TNF-α), and chemokines (CXCL13, CXCL10, CCL2, CXCL11, and CCL25). These inflammatory markers can be used as prognostic indicators for disease progression in pSS. In conclusion, the results from the studies reported in this review indicate that high levels of inflammatory markers may serve as markers for disease progression of pSS, which, in turn, may be valuable in predicting disease outcome.

COVID-19 vaccination and acute infection result in cellular and humoral immune responses with various degrees of protection. While most studies have addressed the difference in humoral response between vaccination and acute infection, studies on the cellular response are scarce. We aimed to evaluate differences in immune response among vaccinated patients versus those who had recovered from COVID-19. This was a prospective study in a tertiary medical centre. The vaccinated group included health care workers, who had received a second dose of the BNT162b2 vaccine 30 days ago. The recovered group included adults who had recovered from severe COVID-19 infection (<94% saturation in room air) after 3-6 weeks. Serum anti-spike IgG and cytokine levels were taken at entry to the study. Multivariate linear regression models were applied to assess differences in cytokines, controlling for age, sex, BMI, and smoking status. In total, 39 participants were included in each group. The mean age was 53 ±14 years, and 53% of participants were males. Baseline characteristics were similar between the groups. Based on multivariate analysis, serum levels of IL-6 (β=-0.4, p<0.01), TNFα (β=-0.3, p=0.03), IL-8 (β=-0.3, p=0.01), VCAM-1 (β=-0.2, p<0.144), and MMP-7 (β=-0.6, p<0.01) were lower in the vaccinated group compared to the recovered group. Conversely, serum anti-spike IgG levels were lower among the recovered group (124 vs. 208 pg/mL, p<0.001). No correlation was identified between antibody level and any of the cytokines mentioned above. Recovered COVID-19 patients had higher cytokine levels but lower antibody levels compared to vaccinated participants. Given the differences, these cytokines might be of value for future research in this field.

There is currently no safe or effective treatment for inflammatory bowel disease (IBD), which is defined as recurrent and persistent intestinal inflammation. Thymic stromal lymphopoietin (TSLP) has been shown to be associated with the pathogenesis of IBD, and the JAK2/STAT5 signalling pathway has demonstrated much promise as a novel therapeutic target for IBD. In this study, we first evaluated levels of TSLP in dextran sodium sulphate (DSS)-induced IBD mice. Second, we applied tezepelumab, an anti-TSLP monoclonal antibody (20 μg per mouse, intraperitoneally), to DSS-induced IBD mice and quantified the signs of histopathological change, intestinal inflammation, and integrity of the mucosal barrier. In addition, the effect of DSS and/or tezepelumab on the phosphorylation of the JAK/STAT pathway was investigated. TSLP expression levels were elevated in DSS-induced IBD mice, whereas TSLP antibody treatment suppressed the pathological features associated with IBD and alleviated intestinal inflammation and mucosal barrier disruption. Moreover, level of phosphorylated JAK2/STAT5 were increased in DSS-induced IBD mice, but were strongly decreased in the presence of tezepelumab. Our findings suggest that targeting TSLP via the JAK2/STAT5 signalling pathway may be an effective approach for the treatment of IBD.

Endometrial cancer (EC) is recognized as the second most common type of cancer among women. Interleukin-37 (IL-37) is a recently discovered member of the IL-1 cytokine family characterized by its anti-inflammatory properties, which are believed to have both anti-tumour and tumorigenic effects. However, the precise role of IL-37 in the development of EC remains largely unknown. In the current study, we aimed to explore genotype and allele frequencies of the IL-37 gene (rs4241122) and measure IL-37 protein levels in patients with EC, with a view to determining the clinical significance in these patients. A total of 105 patients with confirmed EC and 105 healthy controls, aged 31-73, participated in the study. IL-37 serum levels were investigated using an ELISA method, while the frequency of genotypes and alleles of the IL-37 gene was determined using the ARMS-PCR method. The findings demonstrate a significant increase in IL-37 serum levels in EC patients compared to controls (p<0.0001). Moreover, higher levels of IL-37 were strongly associated with unfavourable indices, such as EC grade III, poorly differentiated tumours, and regional spread of tumour cells (p<0.05). However, genotyping of the IL-37 gene revealed no significant difference between the two groups, and there was no association between IL-37 genotype and IL-37 protein level or clinicopathological characteristics (p>0.05). The results of this study suggest that elevated serum levels of may contribute to tumour progression, probably through its immune suppressive activity. Clinically, IL-37 may serve as a promising factor and/or therapeutic target for EC management, although, further studies are warranted.

Spermatogenesis is the complicated process of sperm generation. During this process, spermatogonial cells proliferate and differentiate via meiotic and post-meiotic stages to produce mature sperm. This process is under the regulation of testicular autocrine/paracrine factors. In addition, endocrine factors are crucial to complete spermatogenesis. We aimed to localize granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFR) in testicular cells and further evaluate its involvement in the development of spermatogenesis in vitro. We isolated cells from seminiferous tubule cells of seven-day-old mice and cultured them in vitro using a methylcellulose culture system (MCS), in the presence of GM-CSF and/or testosterone for four weeks. The cells were then examined for markers of different stages of spermatogenesis by immunofluorescence staining and/or qPCR analyses. Our results revealed the presence of GM-CSF and GM-CSFR in testicular cells (premeiotic and meiotic cells as well as somatic cells; Leydig and Sertoli cells). We further demonstrated the development of colonies/spheroids in the MCS which contained pre-meiotic, meiotic, and post-meiotic cells. The addition of GM-CSF to the MCS significantly increased the percentage of pre-meiotic and meiotic cells compared to control. Furthermore, the addition of GM-CSF and testosterone together significantly increased the percentage of cells in the post-meiotic stage compared to the addition of each separately. In conclusion, our results indicate that testicular cells express GM-CSF/GM-CSFR, and that GM-CSF is involved in the development of different stages of spermatogenesis in vitro. Furthermore, testosterone enhances the development of spermatogenic cells and potentiates the effect of GMCSF on the development of post-meiotic cells. These findings provide evidence that GM-CSF and testosterone are involved in the development of spermatogenesis in vitro and in vivo. In brief: Testicular somatic and germ cells express GM-CSF and GM-CSFR. Our study suggests that testicular GM-CSF is involved in the development of spermatogenesis, which is potentiated by testosterone.

The regenerative ability of the liver is essential for maintaining physiological functions and the injury repair process. The biological mechanisms that regulate liver regeneration remain poorly defined. These mechanisms are notable issues in clinical practice that affect the treatment of hepatic loss caused by hepatectomy, hepatic poisoning, or chronic viral infection. Increasing evidence shows that numerous growth factors, cytokines, and metabolic pathways influence the liver regenerative process. Of particular importance are cytokines and growth factors, which affect different stages of liver regeneration. In this review, we summarize the results obtained from studies that focused on the role of growth factors and cytokines in liver regeneration to reflect on the clinical implications and areas for further study.

Background:  Coronavirus infection can induce the production of inflammatory cytokines leading to acute respiratory distress syndrome (ARDS) and death. It is well-established that interferons (IFNs) are essential in regulating the immune response, thus their effects of IFNs on COVID-19 patients should be subject to investigation. This study aimed to investigate the effects of IFN-α alone or in combination with remdesivir in hospitalized COVID-19 patients.

Material and methods:  A multicentre, retrospective study was conducted on COVID-19 patients admitted to three hospitals in Tehran, Iran, from March 20, 2020, to March 18, 2021. The unadjusted and adjusted effects of IFN-α on COVID-19 outcomes were investigated through propensity score matching (PSM) to achieve a 1:1 balanced dataset.

Results: Among 4,782 patients, 3,764 were eligible for the study, including 1,704 patients (45.27%) receiving at least one treatment with IFN-α and 2,060 controls not receiving IFN-α. After PSM, 851 IFN-α patients and 851 controls were recruited in the PSM analysis with a median age of 60.8 (standard deviation [SD]: 16.2 and 60.9 [SD: 17.4]), respectively. The PSM results showed no significant difference between the survival curves of the IFN-α group and the control group (p=0.340). However, the unadjusted impact of IFN-α on the risk of mortality was statistically significant (p=0.043, hazard-ratio: 0.86; 95% confidence interval [CI]: 0.75-0.99). Also, the combination of IFN-α and remdesivir had no significant benefit (HR: 89, 95% CI: 0.74-1.34).

Conclusion: Our findings indicate that subcutaneous administration of IFN-α, with or without remdesivir, does not have any significant impact on COVID-19 mortality and ICU admission. Future clinical trials considering the time, subtype, and form of IFN-α administration are warranted to investigate the potential therapeutic effects of IFN-α on COVID-19.