Investigation of the Role of Interleukin 6 in Vitiligo Pathogenesis

Abstract

ABSTRACT Interleukin-6 (IL6) is involved in pathogenesis of several autoimmune disorders including vitiligo. Hence, we aimed to investigate the association of IL6 −174 G/C and −572 G/C polymorphisms and its transcript levels with vitiligo; to evaluate the effect of IL-6 on normal human melanocyte (NHM) viability and expression of IL6R, MITF and TYR. IL6 -174 G/C and −572 G/C polymorphisms were genotyped by ARMS-PCR and PCR-RFLP respectively in 343 controls and 322 vitiligo patients. IL6 transcript levels were estimated from PBMCs (96 controls and 77 patients) and skin samples (15 controls and 15 patients) by qPCR. NHM viability was assessed by MTT; IL6R, MITF and TYR transcript and protein levels were monitored by qPCR and ICC respectively. Genetic analyses revealed no association of IL6 −174 G/C polymorphism (p> .05) with vitiligo. Analysis of IL6 −572 G/C revealed reduced risk of vitiligo in individuals with GC/CC genotypes compared to GG genotype (p = .010). IL6 expression was significantly increased (p = .0197) in PBMCs of patients. Further, IL6 expression was significantly higher in non-lesional skin compared to controls (p = .009). In-vitro NHM viability was decreased upon IL-6 exposure (10-50 ng/ml; p< .05), with significantly increased IL6R transcript (p = .042) and protein levels (p = .003) however, MITF transcript (p = .0003) and protein levels (p = .016), and TYR transcript levels (p = .001) were significantly decreased. The results suggest that IL6 −572 G/C polymorphism might be associated with vitiligo susceptibility in Gujarat population. Moreover, increased IL6 expression in vitiligo patients and its effect on NHM suggest a potential role in melanocyte biology. Conclusion The results suggest that IL6 − 572 G/C polymorphism might be associated with vitiligo susceptibility in Gujarat population. Moreover, increased IL6 expression in vitiligo patients and its effect on NHM suggest a potential role in melanocyte biology.