FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.
The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011239:Prednisolone / Q000494:pharmacology; D011725:Pyridines / Q000302:isolation & purification / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects; D015375:Receptors, Interleukin-2; D013302:Streptomyces / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D016559:Tacrolimus
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D011725:Pyridines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D011239:Prednisolone; D016559:Tacrolimus