Regulation of Interleukin-12 Production in Human Cells Stimulated withMycobacterium bovisBCG

Interleukin 12 (IL-12) is a monokine which plays a critical role in resistance toMycobacterium tuberculosisinfection. However, little is known about the regulation of IL-12 production by human cells stimulated with BCG. Here we report thatin vitroinfection of human mononuclear cells withM. bovisBCG induces the release of IL-12 protein. We also observed that the ability of BCG to stimulate release of IL-12 from human cells was significantly inhibited by IL-10. The inhibitory effect of IL-10 on the secretion of IL-12 was specific, as it was significantly abolished in the presence of anti-IL-10 neutralizing monoclonal antibody. These results were further confirmed as anti-IL-10 antibodies markedly increased the levels of IL-12, suggesting that BCG-induced IL-10, as well as exogenous IL-10, can regulate IL-12 production by human cells stimulated withM. bovisBCG. Interestingly, IFN-γ production in response to BCG had no significant increase by the addition of neutralizing antibodies to IL-10. Moreover, anti-IL-12 antibodies markedly reduced the levels of IFN-γ produced by BCG-stimulated human cells and abrogated the capacity of anti-IL-10 to increase BCG-induced IFN-γ. These studies are the first to demonstrate a regulatory effect on IL-12 production by human cells infected withM. bovisBCG and at the same time suggest that IL-12 may play an essential role during the human immune response toM. bovisBCG stimulation.