Synergistic effect of pactamycin and sparsomycin on Mycoplasma-induced lethal toxicity of mice.

Pactamycin and sparsomycin, antitumor drugs which act synergistically with endotoxins, also potentiate the lethal toxicity of mice by Mycoplasma fermentans, strain K10. Sparsomycin (50 mug/20 g mouse, injected intraperitoneally 1 h after various doses of M. fermentans) exerted a minimal degree of synergism with few extra deaths, but with prolonged appearance of nonlethal disease. Pactamycin (75 mug in the same protocol) increased susceptibility to Mycoplasma-induced lethal toxicity approximately 1,000-fold. The optimal response was noted when pactamycin was administered in the period between 6 h before and 3 h after the administration of 10(8) colony-forming units of viable mycoplasmas. Doses of 12.5, 25, or 50 mug increased severity of signs, but only 75 mug/mouse produced synergism of the lethal effect. Methylprednisolone partially negated the synergism when injected simultaneously with the pactamycin 1 h after the cells. The lethal synergistic effect occurred with four species of Mycoplasma in addition to M. fermentans.