Interleukin-12 an integral cytokine in the immune response

• Published in: Life Sciences 1996, Vol.58 (8), p.639-654
• Main Authors: Stern, Alvin S., Magram, Jeanne, Presky, David H.
• Format: Article
• Language: English
• Subjects: adaptive immunity; Animals; B-Lymphocytes - immunology; Bacterial Infections - immunology; Cytotoxicity, Immunologic; Humans; Immunity, Cellular - drug effects; Immunity, Cellular - physiology; Interferon-gamma - biosynthesis; interferon-γ; interleukin-12; Interleukin-12 - chemistry; Interleukin-12 - pharmacology; Interleukin-12 - physiology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Lymphocyte Activation; Mycoses - immunology; NK cells; Protozoan Infections - immunology; Receptors, Interleukin - physiology; Receptors, Interleukin-12; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Th 1 cells
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(96)80003-8

Interleukin 12 (IL-12) is a heterodimeric cytokine that is produced primarily by antigen - presenting cells and plays a primary role in the induction of cell-mediated immunity. This function is promoted by the IL-12 induced production of interferon- γ (IFN- γ) from both resting and activated NK and T cells, by the proliferative activity of IL-12 on activated NK and T cells, by enhancing the cytotoxic activity of NK cells, and by supporting cytotoxic T lymphocyte generation. IL-12 and IL-12-induced IFN- γ promote the development of naive T cells into Th 1 cells and the proliferation and IFN- γ secretion by differentiated Th 1 cells in response to antigen. IL-12 has been found to exhibit many of these activities in vivo, as well as in vitro, and thus IL-12 plays an important role in both innate resistance and antigen-specific adaptive immunity to intracellular bacterial, fungal, and protozoan pathogens. Due to its effects on T cells, recombinant IL-12 has been shown to have therapeutic activity in a variety of mouse tumor and infectious disease models and is being evaluated in clinical trials in human cancer patients. IL-12 also appears to play a role in the genesis of some forms of immunopathology, including endotoxin-induced shock and some autoimmune diseases associated with aberrant Th 1 activity. Therefore, IL-12 antagonists may also have therapeutic potential in the treatment of auto immune disorders.