Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1 alpha concentration in uninvolved skin of patients with chronic irritant contact dermatitis

Abstract

Background: Interleukin (IL)-1 alpha and its receptor antagonist IL-1ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1 alpha, IL-1ra, and IL-1 beta, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown. Objective: We studied the association between the polymorphisms IL1A-889 (C -> T) and IL1B-31 (T -> C) and the concentration of IL-1 alpha and IL-1ra in the stratum corneum (SC). Method: In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A-889 and IL1B-31 polymorphisms and determined the amount of IL-1 alpha and IL-1ra on tape strips obtained from uninvolved skin of the volar forearm. Results: The SC IL-1 alpha concentration was 23% and 47% lower in subjects with IL1A-889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B-31 C/C genotype, the IL-1 alpha concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1ra/IL-1 alpha increased twofold in IL1A-889 C/T genotype and threefold in T/T genotype compared with wild type. Conclusions: We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin.