FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.
نویسندگان
چکیده
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.
منابع مشابه
FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics.
FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukubaenis No. 9993 as colorless prism and the molecular formula was determined as C44H69NO12.H2O. The compound suppressed immune responses in vitro and in vivo with mice. This immunosuppressive effect was more potent than that of ciclosporin.
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FK 506 is a powerful immunosuppressant currently being investigated in clinical transplantation. I In vivo administration of this drug resulted in the prolongation of skin, liver, kidney, and heart allografts in large and small animal models.2•3 The immunosuppressive effect has also been shown recently to be effective in the prevention of development of diabetes in BB rats.4 In baboons. treatme...
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FK-506 inhibits Ca(2+)-dependent transcription of lymphokine genes in T cells, and thereby acts as a powerful immunosuppressant. However, its potential therapeutic applications may be seriously limited by several side effects, including nephrotoxicity and neurotoxicity. At present, it is unclear whether these immunosuppressive and toxic effects result from interference with related biochemical ...
متن کامل[The effect of FK 506, an immunosuppressant, on cerebral infarction volume in focal cerebral ischemia in rats].
The effect of FK 506, an immunosuppressant which is widely used in the transplantation of liver, kidney and bone marrow, on cerebral infarction volume in transient focal ischemia was investigated. Focal cerebral ischemia was produced by 2 h occlusion of the left middle cerebral artery in rats. FK 506 (0.3 mg/kg body weight) and vehicle were administered intravenously immediately after induction...
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ورودعنوان ژورنال:
- The Journal of antibiotics
دوره 40 9 شماره
صفحات -
تاریخ انتشار 1987