Effects of verrucarin A and roridin A, macrocyclic trichothecene mycotoxins, on the murine immune system.

Verrucarin A (Ver A) and roridin A (Ror A), macrocyclic trichothecene mycotoxins, were examined for their immunomodulatory effects. Both mycotoxins were administered intraperitoneally at 0.35 mg/kg (1/2 the LD50) in CD-1 mice. Lymphocyte proliferation was studied on days 2, 4 and 7 after animals were dosed with Ver A. After day 2, no significant differences in [3H]thymidine (3H-TdR) incorporation were observed using concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) or lipopolysaccharide (LPS). On day 4 DNA synthesis induced by Con A, PHA and PWM was increased significantly. On day 7, PHA stimulation increased (p less than 0.001) above controls while Con A, PWM and LPS responses were not significantly different. The data indicated that Con A, PHA and PWM responses were time-dependent. Antibody production was evaluated by the hemolytic plaque assay; sheep red blood cells (SRBC) and Ver A were administered simultaneously, and Ver A was given 2 days after SRBC challenge. While spleen weights increased when Ver A was administered with SRBC or when the toxin was given 2 days after antigen, the antibody responses were not altered. In contrast, roridin A decreased PHA stimulation only on day 7 (p less than 0.05). There were no significant effects associated with the other mitogens. Antibody production did not differ significantly following administration of Ror A. Although Ver A and Ror A are equitoxic and structurally similar, their immunomodulatory properties for the given dose differ considerably. These different immunologic responses may be independent of other systemic toxic effects.