Interleukin-10 Gene Research Articles

Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction

Dysregulated inflammation following myocardial infarction (MI) leads to maladaptive healing and remodeling. The study characterized and evaluated a selective formyl peptide receptor 2 (FPR2) agonist BMS-986235 in cellular assays and in rodents undergoing MI. BMS-986235 activated G proteins and promoted β-arrestin recruitment, enhanced phagocytosis and neutrophil apoptosis, regulated chemotaxis, and stimulated interleukin-10 and monocyte chemoattractant protein-1 gene expression. Treatment with BMS-986235 improved mouse survival, reduced left ventricular area, reduced scar area, and preserved wall thickness. Treatment increased macrophage arginase-1 messenger RNA and CD206 receptor levels indicating a proresolution phenotype. In rats following MI, BMS-986235 preserved viable myocardium, attenuated left ventricular remodeling, and increased ejection fraction relative to control animals. Therefore, FPR2 agonism improves post-MI healing, limits remodeling and preserves function, and may offer an innovative therapeutic option to improve outcomes.

What's new in atopic eczema? An analysis of systematic reviews published in 2019. Part 1: Risk factors and prevention.

This review is part of an annual evidence update on atopic eczema (AE), providing a summary of key findings from 18 systematic reviews published in 2019 on AE risk factors and prevention. Parental atopy, particularly AE, is a risk factor for offspring AE, and this risk is augmented both by the number of parental atopic diseases present and the number of affected parents. Low-quality evidence suggests that autumn or winter birth increases childhood AE risk compared with birth in spring. There is some evidence to support filaggrin gene-environment interactions; however, this is limited by small underpowered studies. There is no evidence to suggest that polymorphisms in the -1082, -592 and -819 loci of the interleukin-10 gene increase susceptibility to AE. There is no robust evidence to support a relationship between childhood AE development and either yoghurt consumption in the first year of life, gut microbiota variants, prenatal or infantile paracetamol exposure, maternal antibiotic exposure or air pollution. Three systematic reviews investigated the effect of probiotics given during pregnancy or infancy; although low-quality evidence suggests benefits of combined probiotics, these studies were limited by significant heterogeneity. No relationship between the age at which complementary food and beverages are introduced and the risk of developing AE in infancy was identified. Consistent evidence showed no relationship between human milk feeding and infant AE development, aside from limited evidence suggesting a protective role in those with atopic heredity. This summary of recent evidence related to AE risk factors and prevention highlights the complex aetiology of AE.

Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy.

Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68-1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68-1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68-1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8+ T cells to mediate protection against SIV challenge.

Co-Silencing of Tissue Transglutaminase-2 and Interleukin-15 Genes in a Celiac Disease Mimetic Mouse Model Using a Nanoparticle-in-Microsphere Oral System.

Celiac disease is a chronic inflammatory condition characterized by activation of the immune system in response to deamidation of gluten peptides brought about by tissue transglutaminase-2 (TG2). Overexpression of interleukin-15 (IL-15) in the intestinal epithelium and the lamina propria leads to the dysregulation of the immune system, leading to epithelial damage. The goal of this study was to develop an RNA interference therapeutic strategy for celiac disease using a combination of TG2 and IL-15 gene silencing in the inflamed intestine. TG2 and IL-15 silencing siRNA sequences, along with scrambled control, were encapsulated in a nanoparticle-in-microsphere oral system (NiMOS) and administered in a poly(I:C) mouse model of celiac disease. Single TG2 and IL-15 siRNA therapy and the combination showed effective gene silencing in vivo. Additionally, it was found that IL-15 gene silencing alone and combination in the NiMOS significantly reduced other proinflammatory cytokines. The tissue histopathology data also confirmed a reduction in immune cell infiltration and restoration of the mucosal architecture and barrier function in the intestine upon treatment. Overall, the results of this study show evidence that celiac disease can be potentially treated with an oral microsphere formulation using a combination of TG2 and IL-15 RNA interference therapeutic strategies.

Association between interleukin-32 gene polymorphism and susceptibility to preeclampsia

ABSTRACT Objective: To determine association between IL-32 gene polymorphism, and serum levels of IL-32 and susceptibility to preeclampsia (PE). Methods: The frequency of IL-32 rs9927163 and rs4786370 polymorphisms was determined by PCR-RFLP. Also ELISA was used to determine the levels of serum IL-32. Results: Regarding rs4786370 C/T SNPs, the frequencies of CT, TT genotypes, and T allele were shown to be higher in the PE patients. IL-32 serum level significantly increased in the PE patients. Conclusion: Variety of allele and genotype IL32 rs4786370 as well as a rise in serum level of IL-32 can be regarded as a risk factor for PE.

Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria

IntroductionInterleukin-18 (IL-18) is a pro-inflammatory cytokine, reported to be involved in the initial immune responses against malaria. Genetic variations in the host are an important factor that influences the etiology of malaria at several disease levels. Polymorphisms within the IL-18 gene are associated with susceptibility and clinical outcome of several diseases.MethodsWe genotyped single nucleotide polymorphisms (SNPs) in IL-18 of patients infected with Plasmodium falciparum with varying extent of parasitemia and different age groups.ResultsSNPs rs5744292 (OR = 70.446; 95% CI = 4.318–1149.323; p<0.0001) and rs544354 (OR = 1.498; 95% CI = 1.088–2.063; p=0.013) were found to be significantly associated with parasitemia in P. falciparum-infected patients when compared with healthy control subjects. SNP rs5744292 (OR = 7.597; 95% CI=1.028–56.156; p=0.019) was associated with increased parasite density in infected patients. SNPs rs544354 (OR 0.407; 95% CI=0.204–0.812; p = 0.009) and rs360714 (OR of 0.256; 95% CI=0.119–0.554; p = 0.001) were significantly associated with parasite density in an age-dependent manner, with the risk alleles present more frequently among the younger (1–9 years) patients. Several haplotypes were found to have a significant association with parasitemia. In-vitro expression analysis using luciferase reporter assay showed that SNPs rs1946518 and rs187238 in the IL-18 gene promoter region and rs360728 and rs5744292 in the 3ʹ-untranslated region of the IL-18 gene were associated with enhanced transcriptional activity.ConclusionOur results suggest that polymorphisms within the IL-18 gene are associated with the susceptibility to P. falciparum infection and related parasitemia among groups with different parasite density and across various age groups.

Mechanism of Huanglian Wendan Decoction in intervening IGT IR based on liver cell pyroptosis

To investigate the mechanism of Huanglian Wendan Decoction in intervening impaired glucose tolerance( IGT) rat insulin resistance( IR) based on the pyroptosis pathway of liver cells. The IGT rat model was established by high-fat diet( 20 weeks) combined with high temperature,humidity environment and inactive lifestyle. The experiment was divided into blank group,model group,metformin hydrochloride group( positive group)( 0. 05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group( 7. 8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks,the body weight,body length and abdominal circumferences of all the rats were measured,the Lee&apos; s obesity indexes was calculated,and the levels of fasting plasma glucose( FPG) and 2-hour plasma glucose( 2 hPG) in each group were measured. Serum insulin levels( FINS) and tumour necrosis factor-α( TNF-α) levels were detected by ELISA,and insulin sensitivity index( ISI) and insulin resistance index( IRI) values were calculated. The expressions of cysteinyl aspartate specific proteinase-1( caspase-1),gasdermin D( GSDMD),interleukin-1β( IL-1β) and interleukin-18( IL-18) m RNA and proteins in liver tissues were detected by Real-time PCR and Western blot. Immunofluorescence was used to detect the expressions of caspase-1 and GSDMD protein in liver tissues. Huanglian Wendan Decoction could effectively reduce the weight of model rats,improve abdominal obesity,FINS,IRI and ISI indexes and correct 2 hPG levels. Compared with blank group,TNF-α levels in serum and caspase-1,GSDMD,IL-1β and IL-18 expressions in liver tissue of model control group were increased significantly. Huanglian Wendan Decoction could effectively reduce TNF-α level in serum,regulate the expressions of caspase-1,GSDMD,IL-1β and IL-18 genes and proteins in liver tissues of IGT rats. The above results showed that the occurrence and development of &quot; obesity-IR-abnormal glucose metabolism-type 2 diabetes mellitus&quot; was closely related to inflammatory response and the classical pyroptosis pathway mediated by caspase-1/GSDMD. The mechanism of Huanglian Wendan Decoction in improving IR may be correlated with reduction of the level of inflammatory factors and the alleviation of the state of pyroptosis,and thus reverse the course of IGT.

The Effects of High-intensity Interval Training and Probiotic Consumption on Interleukin-10 and Interferon-gamma Gene Expression of Gut Tissue in an Animal Model of Fatty Liver

Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease, often reported in patients with inflammatory bowel disease. This study aimed to investigate the effects of High-Intensity Interval Training (HIIT) and probiotic use on the expression of interleukin-10 and interferon-gamma genes in intestinal tissue in an animal model of fatty liver. Methods &amp; Materials: In this experimental study, 40 male Wistar rats (weighing 200-250 g) were selected. The study rats were randomly divided into 5 groups, including healthy control, fatty liver, fatty liver + HIIT, fatty liver + probiotic, and fatty liver + HIIT + Probiotics. Oral tetracycline was administered at a dose of 140 mg/kg of body weight (as a solution in 2 mL of water) for 7 days with fatty liver. HIIT was performed on tape 5 times a week for 5 weeks. The obtained data were analyzed using One-way Analysis of Variance (ANOVA) and Tukey post-hoc test at the significant level of P&lt;0.05. Findings: The present research results suggested that the expression of interleukin-10 and interferon-gamma genes in the intestinal tissue of steatosis mice in the fatty liver group was significantly higher than in the healthy control group (P=0.001). HIIT and probiotic use significantly reduced the expression of interleukin-10 and interferon-gamma genes in the intestinal tissue, compared to the fatty liver group (P=0.001). Conclusion: According to the obtained data, HIIT and probiotic consumption can help modulate the expression of genes involved in the innate immune system of intestinal tissue caused by fatty liver.

Association of Interleukin-16 Gene Polymorphisms rs11556218 T/G and rs4072111 C/T with Risk of Breast Cancer in an Iranian Population

Association of Interleukin-16 Gene Polymorphisms rs11556218 T/G and rs4072111 C/T with Risk of Breast Cancer in an Iranian Population

Gene polymorphism and serum levels of interleukin-18 in patients with coronary artery disease and type 2 diabetes mellitus

Background Circulating concentrations of interleukin-18 (IL-18) were shown to be correlated with the vascular events in patients with coronary artery disease (CAD). Objectives To assess the serum levels of IL-18 and its gene polymorphism in CAD and diabetic patients and correlate these findings with clinical, echocardiographic, laboratory, and coronary angiographic findings. Patients and methods This cross-sectional observational study included 180 patients, who were divided according to presence or absence of CAD and type 2 diabetes mellitus into four groups: group I (41 patients), nondiabetic patients without CAD; group II (51 patients), nondiabetic patients with CAD; group III (40 patients), diabetic patients without CAD; and group IV (48 patients), diabetic patients with CAD. Serum levels of IL-18 and its genotyping distributions were measured in all groups and correlated with the angiographic coronary scoring systems. Results Serum IL-18 level was higher significantly in patients with CAD (groups II and IV) than in patients without CAD (groups I and III) (P Conclusion IL-18 is a novel and independent risk factor for CAD, and it is associated with its extent and severity. IL-18 gene polymorphism at 137 G/C site could be a risk factor for development of CAD, presumably by increasing serum IL-18 levels. Individuals carrying the G allele and the G/G genotype of IL-18 have an increased risk to develop CAD.

Reengineering Tumor Microenvironment with Sequential Interleukin Delivery.

Some cytokines can reengineer anti-tumor immunity to modify the tumor micro-environment. Interleukin-27 (IL-27) can partially reduce tumor growth in several animal models, including prostate cancer. We hypothesized that addition of IL-18, which can induce the proliferation of several immune effector cells through inducing IFNγ could synergize with IL-27 to enhance tumor growth control. We describe our findings on the effects of IL-27 gene delivery on prostate cancer cells and how sequential therapy with IL-18 enhanced the efficacy of IL-27. The combination of IL-27 followed by IL-18 (27→18) successfully reduced cancer cell viability, with significant effects in cell culture and in an immunocompetent mouse model. We also examined a novel chimeric cytokine, comprising an IL-27 targeted at the C-terminus with a short peptide, LSLITRL (27pepL). This novel cytokine targets a receptor upregulated in tumor cells (IL-6Rα) via the pepL ligand. Interestingly, when we compared the 27→18 combination with the single 27pepL therapy, we observed a similar efficacy for both. This efficacy was further enhanced when 27pepL was sequenced with IL-18 (27pepL→18). The observed reduction in tumor growth and significantly enriched canonical pathways and upstream regulators, as well as specific immune effector signatures (as determined by bioinformatics analyses in the tumor microenvironment) supported the therapeutic design, whereby IL-27 or 27pepL can be more effective when delivered with IL-18. This cytokine sequencing approach allows flexible incorporation of both gene delivery and recombinant cytokines as tools to augment IL-27’s bioactivity and reengineer efficacy against prostate tumors and may prove applicable in other therapeutic settings.

Interleukin 4 and Interleukin 4 receptor alpha gene variants and risk of atopy - A case control study based assessment

IntroductionIL4 pathway is known to upregulate IgE mediated immune responses and responsible for the manifestation of Atopic disorders. The current study was aimed to elucidate the genetic variations of Interleukin 4 (IL4) and Interleukin 4 receptor alpha (IL4R) genes and their possible association with atopic subjects. MethodsThe well-designed questionnaire was used to collect the subject demographic and clinical details. Biochemical parameters were analysed using Chemiluminescent Immunoassay (CLIA) technique. The genotyping was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). ResultsWe observed a statistically significant difference of serum Immunoglobulin-E (IgE) levels among cases and controls (P<0.05). Subjects harbouring the variant genotypes of I50V and Q576R single nucleotide polymorphisms (SNPs) in IL4R gene showed statistically differential risk towards atopic disorders. However, the variants genotype of 70 bp VNTR polymorphism in IL4 gene showed a protective role towards in predisposition to Atopy. On stratification, the above genetic variants had a significant impact on modifiable and non-modifiable factors associated with the disease. ConclusionOur study demonstrates that increased IgE levels and IL4 gene variants (I50V and Q576R) are significantly associated towards predisposition to allergic disorders in this study population.

Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected Patients Through Single-Cell Transcriptome Sequencing.

Understanding the immunological characteristics of monocytes—including the characteristics associated with fibrosis—in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

IL-33 Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients.

ObjectiveRheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied. This research aimed to investigate the potential of IL-33 gene polymorphisms to serve as biomarkers for disease susceptibility and TNF inhibitor response in RA, AS, and PsA patients.Materials and MethodsIn total, 735 patients diagnosed with RA, AS, and PsA and 229 healthy individuals were enrolled in the study. Genotyping for three single nucleotide polymorphisms (SNPs) within the IL-33 gene, namely, rs16924159 (A/G), rs10975519 (T/C), and rs7044343 (C/T), was performed using polymerase chain reaction amplification employing LightSNiP assays.ResultsIn the present study, the IL-33 rs10975519 CC genotype was associated with a decreased risk of developing RA in females, while the IL-33 rs16924159 polymorphism was associated with the efficacy of anti-TNF therapy and clinical parameters for RA and AS patients. The IL-33 rs16924159 AA genotype correlated with higher disease activity and worse clinical outcomes in RA patients treated with TNF inhibitors, and AS patients carrying the IL-33 rs16924159 AA genotype had higher disease activity and a worse response to anti-TNF therapy. That indicates a deleterious role of the IL-33 rs16924159 AA genotype in the context of RA, as well as AS.ConclusionsThe obtained results suggest that IL-33 gene polymorphisms might be potential candidate biomarkers of disease susceptibility and anti-TNF treatment response in patients with inflammatory rheumatic diseases.

Lack of Effects of the Genetic Polymorphisms of Interleukin-10 in Clinical Outcomes of COVID-19.

Interleukin-10 (IL-10) gene polymorphisms have been associated with severity and outcomes in patients with respiratory and nonrespiratory viral infections. The aim of this study was to assess whether rs1800871 and rs1800872 polymorphisms of IL-10 gene are associated with the clinical outcomes of COVID-19 in a Mexican population. Study subjects were 193 COVID-19 patients. The genotyping was carried out with real-time PCR and serum IL-10 levels were measured with enzyme-linked immunosorbent assay. Logistic regression analysis was used for analysis association with clinical outcomes. There was no evidence of an association between alleles, genotypes, or haplotypes frequencies between patient groups according to severity and outcomes. The rs1800871 and rs1800872 polymorphisms might not be genetic risk factors for severity and mortality for COVID-19 in Mexican mestizos patients from northwest Mexico.

Effects of Probiotic and/or Prebiotic Supplementations on Immune Response, Haematology, Oxidant-antioxidant Biomarkers, and Cytokine mRNA Expression Levels in the Caeca of Broilers Infected with Salmonella

The present study was conducted to evaluate the effects of incorporation of the probiotic mix, prebiotic, and synbiotic supplements on immune response, interleukin-6, interleukin-10, and inducible nitric oxide synthase (iNOS) gene expression, hematology, and oxidant-antioxidant biomarkers of broilers infected with Salmonella Enteritidis and Salmonella Typhimurium mixed infection. A total of 273 commercial Cobb 500 chicks were randomly allocated into seven experimental groups, including NC group: fed only a basal diet (negative control), PC group; fed a basal diet and infected with Salmonellae on 3 rd life day (positive control), ProSa group: administrated probiotic mix in drinking water and then infected with Salmonellae, Presa group: fed prebiotic with basal diet and then infected with Salmonellae, SynSa: received probiotic mix and prebiotic (synbiotic) and then infected with Salmonellae, Pro group: given probiotic mix in feed, and Pre group: basal diet supplemented with prebiotic. The probiotic mix, prebiotic, and synbiotic supplementation significantly increased total IgY levels in the sera of infected birds in comparison to those of positive control. Also, the additives significantly downregulated IL-6 and iNOS gene expressions while they significantly upregulated IL-10 gene expression in the caeca of infected birds, in comparison to those of positive control. Also, the supplementary treatments significantly improved Salmonella-induced changes in hematology and oxidant-antioxidant biomarkers of infected groups. Compared with different supplementary treatments, the synbiotic significantly robust immune response of Salmonellainfected birds when compared with single supplementation of probiotic mix or prebiotic. In conclusion, probiotics, prebiotic, and in particular synbiotic supplements improved immune response, hematological and antioxidative biomarkers of birds experimentally infected with mixed Salmonellae.

Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a chronic infectious disease. Interferon-gamma (IFN-γ) is an important cytokine imparting resistance to mycobacterial diseases. It is believed that IFN-γ and Interleukin-10 (IL-10) play divergent roles in the host immune system against MTB infection. IL-10 is an important inhibitory cytokine and helps balancing the inflammatory and immune responses. IL-10 is involved in down regulation of Th1 cytokines, MHC class II antigen and co-stimulatory molecular expression on macrophages, while IFN-γ results in macrophage activation allowing them to exert the microbicidal role. The objectives were to find out the association of IL-10 (−1082 A/G) and IFN-γ (+874 A/T) single nucleotide polymorphisms (SNPs) with extrapulmonary tuberculosis in ethnic Kashmiri population. A total of 100 extrapulmonary tuberculosis cases and 102 healthy controls were analyzed for IL-10 (−1082 A/G) and IFN- γ (+874 A/T) SNPs using Allele-Specific PCR. We found a significant association of IFN-γ + 874 ‘TT’ genotype with extrapulmonary tuberculosis (p = 0.006) and in case of IL-10 (−1082 A/G) we found a significant association with extrapulmonary tuberculosis under recessive model (GG vs GA + AA) (p = 0.03) in Kashmiri population. IL-10 (−1082 A/G) and IFN-γ (+874 A/T) have a significant association with extrapulmonary tuberculosis in ethnic Kashmiri population.

Reduced IL-37 gene expression and CD8T lymphocytes in patients with metastatic breast cancer.

The exact immunopathological mechanisms in the progression of breast cancer are not clearly understood, but various factors including CD8 T lymphocytes have lethal properties on tumor cells. On the other hand, interleukin-37 (IL-37), as a new member of the IL-1 family, is an anti-inflammatory cytokine. The exact role of IL-37 in breast cancer has not yet been determined. This study aimed to evaluate the CD8T lymphocytes count and IL-37 gene expression in newly diagnosed breast cancer patients with and without metastasis. In this study, blood samples from 36 metastatic and 36 non-metastatic breast cancer patients and 36 healthy individuals as control were collected. After RNA extraction and cDNA synthesis, the relative gene expression was performed using real-time PCR. Also, counting the CD8T lymphocytes was done by flow cytometry technique. The results of this study showed that the gene expression of IL-37 in blood samples of metastatic and non-metastatic breast cancer patients was significantly lower than in healthy individuals (P <0.05). The relative gene expression of the IL-37 in ER+/PR+/HER2+ patients with non-metastatic breast cancer had a significant increase compared to HER2+ patients (P <0.05). Also, CD8T lymphocytes count in the samples of patients including non-metastatic and metastatic breast cancer was significantly decreased compared to the healthy individuals (P <0.05). Our findings provide evidence that IL-37 gene expression and CD8T lymphocytes count, significantly decreased in non-metastatic and metastatic breast cancer. Considering the possible effects of IL-37 on TCD8 cells in tumor immune responses, more research will be done to benefit from the therapeutic effects of this cytokine in the future.

Associations of interleukin-4 and interleukin-4 receptor loci with esophageal squamous cell carcinoma susceptibility

Some functional polymorphisms in immune-regulating genes could affect the development of esophageal squamous cell carcinoma (ESCC). We enrolled 721 patients with ESCC and 1,208 healthy controls to explore the roles of rs2227282 (C > G) and rs2243283 (C > G) loci in the interleukin-4 (IL4) gene and rs1801275 loci in the interleukin-4 receptor (IL4R) gene for the occurrence of ESCC. As for IL4, the single nucleotide polymorphism rs2227282 (C > G) conferred an overall decreased risk for ESCC (adjusted P = 0.005, power = 0.816 in GG vs. CC genetic models). A stratification analysis of IL4 rs2227282 (C > G) and rs2243283 (C > G) and IL4R rs1801275 (A > G) loci with the ESCC risk revealed that the IL4 rs2243283 (C > G) polymorphism was a protective factor for the susceptibility to ESCC in some subgroups (women: power = 0.932 in CG vs. CC and 0.956 in CG/GG vs. CC; subjects aged ≥63 years: power = 0.844 in CG/GG vs. CC; never-smokers: power = 0.893 in CG vs. CC and 0.882 in CG/GG vs. CC; never-drinkers: power = 0.904 in CG vs. CC and 0.862 in CG/GG vs. CC). We also investigated the association of IL4 rs2227282 and rs2243283 and IL4R rs1801275 loci with the lymph node status. However, a null relationship was found. In conclusion, the present study highlighted that IL4 rs2227282 (C > G) and rs2243283 (C > G) loci are protective factors for the occurrence of ESCC.

Impact of IL10, MTP, SOD2, and APOE Gene Polymorphisms on the Severity of Liver Fibrosis Induced by HCV Genotype 4.

Complications of hepatitis C virus (HCV) chronic infection cause ~400,000 deaths worldwide annually. One complication, liver fibrosis, is influenced by host genetic factors. Genes influencing fibrosis include immune, metabolic, oxidative stress, and viral entry genes, such as interleukin 10 (IL10), microsomal triglyceride-transfer protein (MTP), superoxide dismutase-2 (SOD2), and apolipoprotein E (APOE)-encoding genes, respectively. Thus, correlating variations in these genes with HCV-induced fibrosis represents an attractive biomarker for the prognosis of fibrosis severity in chronically infected patients. Here, we aimed to test whether polymorphisms in IL10, MTP, SOD2, and APOE genes correlated with the severity of fibrosis induced by HCV genotype 4 (HCV-gt4) in a cohort of chronically infected Egyptian patients. Our results demonstrate a significant association between the severity of fibrosis and specific SNPs in IL-10, SOD2, and ApoE-encoding genes. Haplotype-combination analysis for IL10, MTP, SOD2, and APOE showed statistically significant associations between specific haplotype combinations and fibrosis severity. Identifying biomarkers correlating with the severity of HCV-gt4-induced fibrosis would significantly impact precision prophylaxis and treatment of patients at risk.