Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite

J Antibiot (Tokyo). 1994 Feb;47(2):208-15. doi: 10.7164/antibiotics.47.208.

Abstract

A potent immunosuppressive activity was found in the culture broth of the fungus Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin) suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction, but had no effect on the growth of human tumor cell lines. It also suppressed the appearance of plaque-forming cells in response to sheep red blood cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after intraperitoneal or oral administration. The metabolite was 10- to 100-fold more potent than cyclosporin A as an immunosuppressive agent of the immune response in vitro and in vivo, and appears to be a candidate for clinical application as a powerful immunosuppressant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / therapeutic use
  • Cyclosporine / immunology
  • Cyclosporine / pharmacology
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / isolation & purification
  • Fatty Acids, Monounsaturated / therapeutic use
  • Fermentation
  • Fungi / metabolism*
  • Humans
  • Immunosuppression
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / immunology

Substances

  • Antifungal Agents
  • Fatty Acids, Monounsaturated
  • Cyclosporine
  • thermozymocidin