Recent advances in the preclinical and clinical immunopharmacology of interleukin-2: emphasis on IL-2 as an immunorestorative agent.
Interleukin-2 (IL-2) is a chemically defined lymphokine (LK) available as mixed human (LK) preparations, as partially purified lymphoblastoid IL-2, or as recombinant human IL-2. Each has different actions dependent on companion LKs showing synergistic interaction (e.g., IL-1 and gamma-interferon (gamma-IFN]). IL-2 acts to expand activated T cells; to activate natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytolytic T cells (CTL); to regulate T-cell ontogeny via actions on prothymocytes and immature T cells; and to induce gamma-IFN and activate tumoricidal macrophages. IL-2 acts via specific cell surface receptors on protein kinase C and cyclic GMP-related mechanisms. While stable, its in vivo half-life is short and its persistence is important for it to induce a response. Toxicities include an influenzia-like syndrome, anemia, eosinophilia, and fluid accumulation. In vivo actions include augmentation of cytotoxic responses at high doses, T-cell adjuvant actions, and T-cell restorative actions at midrange doses and at low doses with companion LKs. Antitumor responses in man and animals occur, but irregularly. They are maximized by the concomitant use of LAK cells, cytoreductive therapy, antisuppressor cell therapy, and regional or persistent administration. IL-2 offers hope for more effective therapy of cancer and a variety of immunodeficiency diseases involving IL-2 defects, including AIDS, viral infections, and autoimmune diseases.
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000628:therapy
D007376:Interleukin-2; D007371:Interferon-gamma