Impaired murine resistance to Salmonella typhimurium following oral exposure to the trichothecene T-2 toxin.

On orally exposing Salmonella-resistant C3H/HeN mice to the trichothecene T-2 toxin (1 mg/kg body weight), challenging with Salmonella typhimurium, and continuing to dose with T-2 toxin on alternate days for 3 wk, the LD50 for the organism decreased by five orders of magnitude, in comparison with control mice not treated with T-2 toxin. In the absence of S. typhimurium, T-2 toxin did not cause lethal effects when administered at this level. Increased mortality in response to S. typhimurium challenge was dependent on T-2 toxin dose in the range 0 to 1 mg/kg for this regimen. The toxin did not significantly affect intestinal infection but did increase splenic counts in mice challenged with a range of S. typhimurium doses and also accelerated body-weight loss in infected animals. Mice challenged with the organism exhibited similar mortality when T-2 toxin treatment was begun 1 day prior to infection or at 5 or 9 days after infection. A time-related decrease in mortality, relative to that found for the standardized co-challenge described above, was observed when T-2 toxin administration was begun at 9, 13 or 23 days after infection. The results indicated that, depending on the challenge dose of the organism, both early and late phase acquired immune response to S. typhimurium could be impaired by T-2 toxin. Markedly enhanced susceptibility to gram-negative bacterial infection is another manifestation of trichothecene toxicity and may be an important aetiological factor in animal health problems that are associated with these mycotoxins.