Cyclomunine: a potent inhibitor of rat and canine lymphocytes

In the present study we examined the effect of a recently isolated hexacyclodepsipeptide, Cyclomunine (Servier, France), on certain parameters which assess cellular and humoral immunity in the rat and dog. Our data establish Cyclomunine as a potent in vitro inhibitor of 3H-thymidine incorporation by lymphocytes. The concentrations of Cyclomunine required to abrogate mitogen or allogeneic lymphocyte stimulated 3H-thymidine incorporation was greater in the dog than in the rat, 15 micrograms/ml versus 10 micrograms/ml, respectively, to achieve greater than 99% inhibition. Little cytotoxicity was noted at concentrations below 25 micrograms/ml. Oral administration of Cyclomunine to rats (50 mg/kg dissolved in corn oil) did not significantly alter white blood cell count, lymphocyte-polymorphonuclear cell differential, body weight, or histological architecture of the liver, spleen, lymph node or kidney. Our results show that in vitro, Cyclomunine is highly effective in suppressing lymphocyte proliferation. In vivo, Cyclomunine appears to have little myelosuppressive effect a property shared with Cyclosporin A. Cyclomunine may hold promise as a clinically useful immunosuppressive agent.