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.


CONCLUSIONS
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.
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000097:blood / Q000276:immunology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008925:Mites / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*