Background and Objective: Nickel sulphate stimulates the proliferation of lymphocytes in nickel-allergic subjects. However, nickel-induced stimulation of lymphocytes from control persons without clinical symptoms of nickel allergy has also been reported. The aim of the present study was to correlate T cell activity, measured by DNA synthesis and the expression of Th1 [interleukin (IL)-2, tumour necrosis factor (TNF)-β and interferon (IFN)-γ] and Th2 (IL-4) cytokines, in short-term (up to 72 h) culture of nickel-stimulated peripheral blood mononuclear cells (PBMC) from nickel-allergic patients compared to control subjects. Methods: DNA synthesis was measured by the incorporation of [methyl-3H]thymidine. The production of IL-2, TNF-β, IFN-γ and IL-4 was measured in the supernatants of the cultures by ELISA. In situ hybridization for mRNA was performed using oligonucleotide probes for IL-4, IFN-γ and TNF-β in cell smears. Results: Already after 24 h and proceeding through the remaining culture period, there was a statistically significant (p < 0.001) difference in the concentrations of IL-2 between patients and controls. There was a significant (p < 0.01) difference in DNA synthesis (stimulation index) between the patients and control subjects at 72 h, and also at the same time a difference in the concentrations of TNF-β (p < 0.05) and IL-4 (p < 0.01). In the in situ hybridization study, TNF-β was found to be the only one of the studied cytokines that differed between the nickel-allergic and control subjects, this difference being most evident at 72 h (p < 0.01). Conclusions: Our results indicate a difference between nickel-allergic and non-allergic subjects in the synthesis of DNA and production of cytokines when PBMC are stimulated by nickel sulphate, and IL-2 may be regarded as a critical and early-occurring cytokine
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