Impact of IL-10 and IL-12B single nucleotide polymorphisms on circulating cytokine level in development of Hashimoto's thyroiditis

Abstract

ABSTRACTHashimoto's thyroiditis (HT) is an organ-specific, mainly Th1 autoimmune disorder. New evidence has accumulated for involvement of Treg-produced cytokines. Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with antagonistic effect on Th differentiation. This study was designed to investigate the correlation of circulating IL-10 and IL-12p40 with their genotypes in 124 HT patients in different stages of disease. The IL-10 and IL-12p40 circulating level in the serum of HT patients and healthy controls was determined by enzyme-linked immunosorbent assay. Genotyping for the 3’UTR A/C IL12B polymorphism was performed using restriction fragment length polymorphism–polymerase chain reaction and genotyping for −1082 A/G by amplification refractory mutation system (ARMS)-PCR. The results showed significantly enhanced IL-12p40 serum quantity both in euthyroid and hypothyroid stages compared to controls and insignificantly decreased level after levothyroxine treatment. Regarding the 3’UTR A/C IL12B polymorphism, a significantly higher frequency of the AA genotype was observed in HT patients than in healthy individuals. The serum IL-10 level was significantly increased in hypothyroid HT patients compared to controls and euthyroid patients. Stratification based on the −1082 A/G polymorphism revealed a significantly enhanced level of circulating IL-10 in hypothyroid patients with a GG genotype compared to AA and AG genotypes. There were also significant differences between the circulating IL-10 quantity in hypo- and euthyroid patients with GG genotypes. In conclusion, the IL-12p40 and IL-10 serum level in HT patients was dependent on the genotype and HT stages, suggesting that enhanced IL-10 serum level in combination with enhanced IL-12p40 is associated with hypothyroidism in HT development.