Contact Dermatitis 2008: 58: 263–268 Printed in Singapore. All rights reserved # 2008 The Authors Journal compilation # 2008 Blackwell Munksgaard CONTACT DERMATITIS Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1a concentration in uninvolved skin of patients with chronic irritant contact dermatitis CINDY M. DE JONGH 1 ,LIUBOV KHRENOVA 2 ,SANJA KEZIC 1 ,THOMAS RUSTEMEYER 3 ,MAARTEN M. VERBERK 1 AND SWEN M. JOHN 2 1 Coronel Institute of Occupational Health, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands, 2 Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrueck, D-49069 Osnabrueck, Germany, and 3 Department of Dermatology, VU University Medical Centre, 1081 HV Amsterdam, the Netherlands Background: Interleukin (IL)-1a and its receptor antagonist IL-1ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1a, IL-1ra, and IL-1b, 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-1a 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-1a and IL-1ra on tape strips obtained from uninvolved skin of the volar forearm. Results: The SC IL-1a 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-1a concentration was 51% lower compared with C/T and T/T geno- types. The ratio IL-1ra/IL-1a 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. Key words: interleukin-1; single nucleotide polymorphism; stratum corneum; tape stripping. # Blackwell Munksgaard, 2008. Accepted for publication 19 November 2007 Chronic irritant contact dermatitis (CICD) is a fre- quently occurring occupational disease, mainly caused by repetitive contact of the skin to irritants and most often located on the hands and fore- arms. The eczematous reaction is characterized by dryness, redness, scaling, and hyperkeratosis (1). The mechanism of the development of CICD and the predisposing factors for this skin disease are not well understood. Cytokines and chemo- kines play an important role in skin inflammation by orchestrating cutaneous inflammatory and repair processes (2). Upon an external insult, ker- atinocytes produce a wide variety of inflammatory mediators, e.g. granulocyte–macrophage colony- stimulating factor, interferon-g, interleukin (IL)- 1a, IL-1b, IL-6, IL-8, and tumour necrosis factor-a, resulting in a pro-inflammatory cascade reaction (2, 3). To counteract this inflammatory response, anti-inflammatory cytokines are also produced, e.g. IL-1ra and IL-10 (2, 4). The bal- ance between pro- and anti-inflammatory cyto- kines is important for the extent and duration of the individual inflammatory response (2). In genes encoding cytokines, several poly- morphisms were found, which influence the levels of these proteins (5). These genetic variants might