Nickel-induced IL-10 down-regulates Th1- but not Th2-type cytokine responses to the contact allergen nickel


J. T. Minang, Department of Immunology F5, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden


Whereas the involvement of Th1- and Th2-type cytokines in contact allergy to nickel (Ni) is well documented, the role of the regulatory cytokine IL-10 is less clear. We therefore investigated the impact of IL-10 on Ni-induced Th1- (IFN-γ) and Th2-type (IL-4 and IL-13) cytokine responses in human peripheral blood mononuclear cells (PBMC). PBMC from 15 blood donors with reactivity to Ni (Ni-PBMC) and 8 control donors devoid of reactivity (control PBMC) were stimulated with Ni and the frequency of cytokine-producing cells and the levels of secreted cytokines were analysed by ELISpot (IL-4, IL-13 and IFN-γ) and ELISA (IL-10, IL-13 and IFN-γ), respectively. The Ni-induced response was further assessed in the presence of recombinant IL-10 (rIL-10) or neutralizing antibody to IL-10 and the phenotype of the Ni-specific cytokine-producing cells regulated by IL-10 was determined by cell depletion experiments. Ni induced IL-10 production in Ni-PBMC (mean, (range); 33·1 pg/ml (0–93·4 pg/ml)) but not control PBMC (2·2 pg/ml (0–14·9 pg/ml)) (= 0·002). Ni also induced significant production of IL-4, IL-13 and IFN-γ that correlated with the IL-10 response. Addition of rIL-10 down-regulated the Ni-induced production of all cytokines but with a more pronounced effect on IFN-γ. However, neutralization of Ni-induced IL-10 enhanced the levels of IFN-γ induced by Ni (= 0·004) but did not affect the number of IFN-γ-producing cells or the production of other cytokines. Cell depletion experiments suggested that the Ni-specific IFN-γ (and Th2-type cytokine) producing cells were CD4+ T cells. The impact of IL-10 on Ni-induced IFN-γ responses by CD4+ T cells suggests that an important role of IL-10 in vivo is to counteract the allergic reactions mediated by Th1-type cytokines.