IL-12 affects Dermatophagoides farinae-induced IL-4 production by T cells from pediatric patients with mite-sensitive asthma.

BACKGROUND: IL-12 is a critical cytokine in the regulation of immune responses produced by phagocytic cells exposed to microorganism infection. OBJECTIVE: We sought to study the effect of low doses and high doses of IL-12 on TH1 versus TH2 cytokine expression to elucidate the etiology of mite antigen-sensitive bronchial asthma in infants. METHODS: We studied the effect of IL-12 on Dermatophagoides farinae (Df) antigen-induced IL-4 production and subsequent production of IgE by PBMCs from pediatric patients with asthma. RESULTS: Simultaneous addition of 1 to 10 ng/mL IL-12 to cultures enhanced Df-induced IL-4 production, although low doses (0.05 to 0.1 ng/mL) of IL-12 downregulated IL-4 production. Endogenous IL-12 is required for such production. These phenomena were not observed in Df-stimulated control PBMCs. In contrast, on stimulation with the same dose of Df, IFN-gamma production by patient PBMCs was enhanced in a dose-dependent fashion by addition of IL-12. Quantification analysis of RT-PCR-amplified DNA fragments by laser-induced fluorescence showed that a high dose of IL-12 augments mRNA expression for IL-4 protein synthesis, whereas a low dose of IL-12 inhibits IL-4 mRNA expression, and that the signal of mRNA for IFN-gamma protein synthesis was increased on Df stimulation in a dose-dependent fashion. Df-induced in vitro production of IgE and Df-specific IgE in serum from severe combined immunodeficient mice reconstituted with PBMCs were increased by treatment with high doses of IL-12, whereas low doses of IL-12 inhibited that production. The combined results indicate that at a low dose of IL-12, IL-4 and IFN-gamma production was regulated reciprocally; however, at high doses of IL-12, cells produced IL-4 and IFN-gamma simultaneously, and neither cytokine was regulated. CONCLUSION: Low-dose and high-dose IL-12 induce TH1 responses, and high-dose IL-12 induces both TH1 responses and TH2 or TH0 responses. Consequently, the IL-4 production may overcome TH1-type cell activation of IgE production in patients with mite-sensitive bronchial asthma.