Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes.

P HAGOCYTIC CELLS and natural killer (NK) cells are among the effector cell types of innate resistance that represent a first line of defense against infections or foreign pathogens. During the early inflammatory response to an infection, regulatory interactions between these cell types take place, mostly mediated by cytokines that regulate activation and migration of phagocytic cells and NK cells. One of these mechanisms, often referred to as T-cell-independent macrophage activation, is observed in T-cell-deficient SCID mice.' When these animals are infected with Listeria monocytogenes or other bacteria, a rapid production of interferon-y (IFN-y) is observed that acts as a potent activator for phagocytic cells, increasing their bacteriocidal activity as well as their ability to produce cytokines. The major factor produced by the infected phagocytic cells and responsible for induction of production of IFN-y is interleukin-l2 (IL12), a heterodimeric cytokine that is a potent inducer of cytokine production, particularly IFN-y, in T and NK cells, a growth factor for preactivated T and NK cells, and an enhancer of cytotoxic activity in both CD8' T cells and NK cell^."^ IL-12 is produced by phagocytic cells, B cells, and other antigen-presenting cell (APC) types.' In addition to its role in the phagocytic cell activation mechanism early in the inflammatory response to infections, APC-produced IL12 has an obligatory role for the generation of T-helper type I (Thl) cells (producing IL-2 and IFN-y)*"" and for optimal differentiation of cytotoxic T lymphocytes (CTL)." The early decision towards Thl and Th2 cells in the immune response is dependent on the balance between IL-12, which favors Thl responses, and IL-4, which favors Th2 responses."'