Interleukin-12: a bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency.
Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine originally identified as a product of EBV-transformed B cell lines. Monocyte/macrophages are the physiologically most relevant producers of IL-12, in response to both Gram-positive and -negative bacteria, bacterial products, and intracellular parasites. Although IL-12 has an enhancing effect on the survival and growth of early hematopoietic progenitor cells, most of the IL-12 biological activity has been described on T and NK cells, on which it induces production of lymphokines, primarily IFN-gamma, enhances cytotoxic activity, and, in cooperation with other stimuli, increases proliferation. IL-12 is an inducer of development of T helper type 1 (Th-1) cells and the equilibrium between IL-12 and IL-4 is probably important for the balance in vivo between Th-1 and Th-2 responses. IL-12 has an important role in the host resistance to infection, in particular to intracellular pathogens, by activating macrophages through induction of IFN-gamma from NK and T cells and by enhancing cell-mediated immune responses, dependent on Th-1 cell development. Peripheral blood mononuclear cells from HIV-seropositive individuals are impaired in their ability to produce IL-12 in response to bacterial stimulation, and IL-12 restores in vitro some of the depressed immunological functions, suggesting that a defect in IL-12 production may have a pathogenic role in the immunodeficiency of HIV-infected individuals. Natural IL-12 appears to provide a regulatory link between innate resistance and the development of the antigen-specific adaptive immune response and the recombinant protein has therapeutic potential because of its activity against tumors and infections and its effectiveness as an adjuvant enhancing cell-mediated immunity in vaccination.
Chehimi
J
J
Children's Hospital of Philadelphia, Pennsylvania.
Trinchieri
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D006133:Growth Substances; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000276:immunology*; D011528:Protozoan Infections / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology; D053707:Receptors, Interleukin-12; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D006133:Growth Substances; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12