Cytokines acting on or secreted by macrophages during intracellular infection (IL-10, IL-12, IFN-gamma)

The three cytokines IL-12, IL-10, and IFN-gamma have important and cross-regulatory roles in infection. In the past year, much progress has been made in the understanding of the cellular and molecular mechanisms involved in the regulation (and cross-regulation) of these three cytokines and their role in pathology. IL-12 is rapidly produced after infection and acts as a proinflammatory cytokine eliciting the production, by T cells and natural killer cells, of IFN-gamma which activates phagocytic cells. The production of IL-12 is strictly regulated by negative and positive feedback mechanisms. If IL-12 and IL-12-induced IFN-gamma are present during early T cell expansion in response to antigen, Th1 cell generation is favored and the generation of Th2 cells is inhibited. Thus, IL-12 is also a potent immunoregulatory cytokine which promotes Th1 differentiation and is instrumental in the Th1-dependent resistance to infections by bacteria, intracellular parasites, fungi, and certain viruses. Viruses inducing a permanent or transient immunodepression, such as HIV and measles, may act, in part, by suppressing IL-12 production.