Effects of interaction between Escherichia coli verotoxin and lipopolysaccharide on cytokine induction and lethality in mice

In Escherichia coli O157 infections, verotoxins (VT) play a critical role in causing the disease, although other factors such as lipopolysaccharide (LPS) and inflammatory cytokines may affect the progression and course of the disease. The present study examined the roles of VT and LPS in induction of serum cytokines and lethality in mice. LD50 of VT2 (13 ng) was c. 10(4)-fold smaller than that of LPS (400 mu g). Although the lethal toxicity of these toxins was examined in several experimental conditions, such as VT2 (5, 10, 20, 40ng/mouse) alone or in combination with LPS (100 mu g/mouse) at various times (-2 days to +2 days), no evidence of synergy was observed. VT2 did not augment LPS-induced tumour necrosis factor-alpha (TNF-alpha) or interleukin-6 production, and conversely suppressed TNF-alpha production when it was injected 2 days before LPS challenge. The data failed to indicate either synergic or additive effects of VT and LPS on cytokine production or lethality in mice. In contrast, antagonistic interactions were clearly observed in cytokine production in certain conditions. The results suggested that these toxins may be co-operatively involved in the pathology of VT-related diseases, but not through synergic interactions.