Immunoregulation by interleukin‐12

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 granulocyte‐macrophage colony‐stimulating factor (CM‐CSF) and interferon‐γ (IFN‐γ) or inhibited by IL‐10. 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‐γ by NK and later by T cells. This IFN‐γ 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‐γ and IL‐10 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.