Pretreatment of mice with lipopolysaccharide (LPS) or IL-1 beta exerts dose-dependent opposite effects on Shiga toxin-2 lethality

Haemolytic uraemic syndrome (HUS) has been closely associated with infectio n with a group of Shiga toxin-producing enterohaemorrhagic Eschericchia col i in young children. Shiga toxins (Stx) have been implicated as pathogenic agents of HUS by binding to the surface receptor of endothelial cells. LPS is a central product of the Gram-negative bacteria and several reports have documented that both LPS and Stx are important for disease development. In this study the reciprocal interactions between LPS and Stx2 are analysed i n a mouse model. The results demonstrated that LPS was able to reduce or en hance Stx2 toxicity, depending on the dose and the timing of the injection. The involvement of the main early cytokines induced by LPS, tumour necrosi s factor alpha (TNF-alpha) and IL-1 beta, in those LPS opposite effects on Stx2 toxicity was evaluated. Stx2 toxicity was enhanced by in vivo injectio n of murine TNF-alpha and low doses of murine IL-1 beta. However, at higher doses of IL-1 beta which induced corticosteroid increase in serum, Stx2 le thality was decreased. Considering that dexamethasone and IL-1 beta reprodu ce the LPS protective effects, it is suggested that endogenous corticostero ids secondary to the inflammatory response induced by LPS, mediate the prot ection against Stx2. It can be concluded that the fine equilibrium between proinflammatory and anti-inflammatory activities strongly influences Stx2 t oxicity.