The two faces of interleukin 12: a pro-inflammatory cytokine and a key immunoregulatory molecule produced by antigen-presenting cells.

Abstract

Interleukin 12 (IL-12) is produced by phagocytic cells, antigen-presenting cells and B lymphocytes in response to bacteria or intracellular parasites. IL-12 acts on T and natural killer (NK) cells inducing: production of cytokines, particularly gamma-interferon (IFN-gamma); proliferation; and enhancement of cell-mediated cytotoxicity. Early in infection, IL-12 acts as a proinflammatory cytokine and induces IFN-gamma production by NK and T cells. IFN-gamma activates the phagocytes and increases their ability to produce IL-12. Unlike IFN-gamma, IL-10, IL-4, IL-13 and transforming growth factor beta are negative regulators of the production and activity of IL-12. IL-12 sets the stage for the ensuing adaptive immune response by stimulating the generation of T helper 1 (Th1) cells. It is likely that the balance between IL-12 (favouring a Th1 response) and IL-4 (favouring a Th2 response) determines the eventual outcome of the Th1/Th2 dichotomy during an immune response. HIV-infected patients have a deficient production of IL-12, even at early stages of the disease. However, exogenous IL-12 can improve the deficient immune responsiveness of these patients' T and NK cells in vitro, suggesting a possible role of the IL-12 deficiency in HIV disease pathogenesis and a potential therapeutic role of IL-12 both against opportunistic pathogens and HIV infection itself.