FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro

J Antibiot (Tokyo). 1987 Sep;40(9):1256-65. doi: 10.7164/antibiotics.40.1256.

Abstract

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.

MeSH terms

  • Animals
  • Cyclosporins / pharmacology
  • Cytotoxicity, Immunologic / drug effects
  • Female
  • Humans
  • Immunosuppressive Agents / isolation & purification
  • Immunosuppressive Agents / pharmacology*
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Prednisolone / pharmacology
  • Pyridines / isolation & purification
  • Pyridines / pharmacology
  • Receptors, Immunologic / drug effects
  • Receptors, Interleukin-2
  • Streptomyces / analysis*
  • T-Lymphocytes, Cytotoxic / drug effects
  • Tacrolimus

Substances

  • Cyclosporins
  • Immunosuppressive Agents
  • Pyridines
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Interferon-gamma
  • Prednisolone
  • Tacrolimus