Structure of Il-12 and Its Receptor

Interleukin-12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (monocytes, macrophages, dendritic cells, and B cells). Its production is stimulated by bacteria, bacterial products, and intracellular parasites and enhanced by priming with granulocytemacrophage colony-stimulating factor (CM-CSF) and interferon-y (IFN-’y) or inhibited by IL-b. The major biological activity of IL-12 is on T and natural killer (NK) cells in which it increases cytokine production, proliferation, and cytotoxicity. Its production occurs several hours after exposure to infectious agents, which induces a rapid production of IFN-y by NK and later by T cells. This IFN-’y potentiates antigen-presenting cell functions important in clearing infectious agents (phagocytosis, oxidative burst, and production of nitrous oxide) and also increases further production of IL-12. IL-12 has been clearly demonstrated to be important in the generation of CD4 and CD8 type 1 T cells both in vivo and in vitro. Our data reveals that IL-12 primes naive T cells for high IFN-’y and IL-b production, whereas IL-4 is required for IL-4 priming, thus suggesting that these genes and possibly others are independently regulated. IL-12 is therefore involved in the skewing of cytokine production toward a type 1 and has been implicated in being involved in selective mechanisms of established T cells. It is now becoming clear that the IL-12 acts as both a proinflammatory cytokine and an immunomodulator and therefore bridges the innate and adaptive immune responses. J. Leukoc. Biol. 59: 505-511; 1996.