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

Summary 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)) ( P  = 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 ( P  = 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.