Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls - Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge

Exposure to nickel is a major cause of allergic contact dermatitis which is considered to be an inflammatory response induced by antigen-specific T ce lls. Here we describe the in vitro analysis of the nickel-specific T-cell-d erived cytokine response of peripheral blood mononuclear cells from 35 nick el-allergic and 30 non-nickel-allergic individuals. Peripheral blood mononu clear cells were stimulated with 10(-4) and 10(-5) mol/l NiSO4 for 6 days a nd then additionally with ionomycin and phorbol myristate acetate for 24 h, Culture supernatants were analysed for interleukin-4 (IL-4), IL-5, interfe ron-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) by quant itative ELISA. The analysis showed that the synthesis of IL-4 and IL-5 but not of IFN-gamma or TNF-alpha was significantly higher in the nickel-allerg ic individuals. The finding of preferential synthesis of Th2 cytokines was somewhat of a surprise, since previous studies have suggested a Th1 respons e in nickel-mediated allergic contact dermatitis, Subsequently, the nickel- allergic individuals were randomized to experimental exposure to nickel or vehicle in a double-blind design. A daily 10-min exposure of one finger to 10 ppm nickel solution for 1 week followed by 100 ppm for an additional wee k evoked a clinical response of hand eczema in the nickel-exposed group. Bl ood samples were drawn on days 7 and 14 after the start of this exposure to occupationally relevant concentrations of nickel. No statistically signifi cant differences were observed in the nickel-induced in vitro cytokine resp onse during the exposure period. Our results indicate the possibility that IL-4 and IL-5 are involved in the pathogenesis of nickel-mediated contact d ermatitis.