Associação entre polimorfismos de IL-10 E células T CD4+CD25+FOXP3+ em escolares asmáticos

Abstract

Introduction: asthma is the most common chronic illness in childhood. In Brazil, the disease presents high rates of prevalence and incidence, according to DATASUS data. Inflammation and hyperresponsiveness in asthma are triggered by various cells of the immune system in the airways. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and its levels are generally decreased in asthmatics. Some single nucleotide polymorphisms (SNPs) of the IL-10 gene were associated with asthma. In addition, IL-10 may potentiate the differentiation of regulatory T cells (Tregs). Studies have shown that an imbalance in the number and / or function of these cells may be related to the development of asthma. Objectives: the main objective of this study was to evaluate the association between IL-10 gene polymorphisms and asthma severity in a sample of schoolchildren. As secondary objectives, we investigated the association between IL-10 genotypes and the frequency of regulatory T lymphocytes (Tregs) and the association between IL-10 genotypes and IL-10 protein levels. Methods: four polymorphisms of the IL-10 gene (rs1518111, rs3024490, rs3024496, rs3024491) were genotyped in asthmatic schoolchildren and controls from Porto Alegre (Brazil) using real-time PCR. Tregs cells and IL-10 protein levels were analyzed in peripheral blood mononuclear cells by flow cytometry. Asthma severity was defined according to the GINA guideline. Results: one hundred twenty-three asthmatic schoolchildren and fifty-eight controls participated in the study. The SNP rs3024491 (T allele) was associated with the severity of asthma, presenting a higher frequency in patients in the moderate asthma group. The T allele of variant rs3024491 also showed an association with reduced IL-10 levels (p = 0.01) and increased Tregs cells frequency (p = 0.01). The other variants did not present consistent associations. Conclusions: our results suggest that moderate / severe asthma is associated with a higher frequency of the T allele in the SNP rs3024491. In addition, the variant rs3024491 (TT) was associated with a reduction in IL-10 production and an increase in the percentage of Tregs cells, suggesting possible mechanisms that influence the severity of asthma.