Synergistic interaction between the trichothecene T-2 toxin and Salmonella typhimurium lipopolysaccharide in C3H/HeN and C3H/HeJ mice

Abstract

The capacity of the trichothecene T-2 toxin to alter resistance to bacterial lipopolysaccharide (LPS) was examined in the mouse. Both LPS-susceptible (C3H/HeN) and LPS-resistant (C3H/HeJ) mouse strains exhibited markedly enhanced mortality when a single oral dose of T-2 toxin (1 mg/kg) was coadministered with a subacute i.p. dose of Salmonella typhimurium LPS. In the absence of LPS, T-2 toxin did not cause lethal effects when administered at this level. LD50 values for LPS decreased by 14-fold and 4.5-fold upon co-administration with T-2 toxin (1 mg/kg) in C3H/HeN and C3H/HeJ mice, respectively. Increased mortality was accompanied by an impaired splenic response to LPS in C3H/HeN mice. C3H/HeN mice pretreated with a sublethal dose of LPS 24 h prior to T-2 toxin administration also exhibited significantly increased susceptibility to T-2 toxin. Histopathological assessment revealed that the liver and spleen of mice exposed to T-2 toxin and LPS exhibited extensive cell death as compared to control mice treated with T-2 toxin or LPS only. The results suggest that bacterial LPS and trichothecenes such as T-2 toxin interact synergistically. This interaction may contribute to increased mortality that has been observed previously in animals challenged with Salmonella and T-2 toxin.