Activation of mononuclear cells by interleukin-12: An in vivo study in chimpanzees

Interleukin (IL)-12 is considered a central regulator of host resistance ag ainst a variety of pathogens. Therefore, IL-12 has been advocated as a pote ntial therapeutic agent in infections. To determine the in vivo effects of IL-12 on mononuclear cells involved in the host immune response, four chimp anzees received an intravenous injection of recombinant IL-12 (1 mu g/kg). IL-12 induced a sustained decrease in lymphocyte counts, with decreases in CD3+/CD4+ and CD3+/CD8+ cells, while monocyte counts showed a transient inc rease. IL-12 injection resulted in a shift toward a Th1-mediated immune res ponse as indicated by increased interferon-gamma production during whole-bl ood stimulation, while not influencing IL-4 production. IL-12-induced activ ation of NK cells and phagocytes, as indicated by increased NK cell cytotox icity and increased plasma levels of granzymes A and B and of chitotriosida se activity. These data support the hypothesis that IL-12 may serve as a us eful therapeutic agent in infections where a cell-mediated response is prot ective.