The effects of cyclosporin A on non-T cell components of the immune system.
Cyclosporin A (CsA) is a potent inhibitor of cytokine (IL-2-IL-6, IFN gamma) production by CD4+ T lymphocytes stimulated via the T cell antigen receptor pathway. This action results in indirect inhibitory effects on the growth and differentiation of B lymphocytes (IL-4 and IL-6). Using experimental models, it has also been shown that the functional activities of mononuclear phagocytes (IFN-gamma) and other antigen-presenting cells, production of mast cells (IL-3) and eosinophils (IL-5) and the activity of natural killer (NK) cells may be inhibited indirectly by CsA. In addition, however, CsA blocks B cell responses to Ca(2+)-dependent signals (e.g., anti-IgM) downstream of phosphatidyl inositol diphosphate hydrolysis; Ca(2+)-independent responses (e.g., to LPS or IL-4) are largely unaffected. In general terms, the functions of macrophages are unchanged or reduced in the presence of CsA. These include phagocytic activity in vitro and in vivo, chemotactic migration, superoxide and H2O2 production, protein (including monokine) secretion and MHC gene product expression. Antigen presentation (e.g., by epidermal Langerhans cells) may be affected, especially at high drug concentrations. There is recent evidence that CsA inhibits mediator (histamine and prostaglandin) release from human mast cells and that mucosal mast cell numbers may be diminished in CsA-treated animals exhibiting graft-versus-host disease or helminth infections.
Thomson
A W
AW
Department of Surgery, University of Pittsburgh, PA 15213.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E; D016572:Cyclosporine; D010100:Oxygen; D002118:Calcium