DIFFERENCES IN CYTOKINE RESPONSE AND INDUCTION OF NITRIC-OXIDE SYNTHASE IN ENDOTOXIN-RESISTANT AND ENDOTOXIN-SENSITIVE MICE AFTER INTRAVENOUS GRAM-NEGATIVE INFECTION

Previous reports have suggested that the endotoxin-resistant C3H/HeJ s train of mouse is more susceptible to infection than is the endotoxin- sensitive parent strain, C3H/HeN, although they have never been compar ed in an i.v. model of sepsis. We therefore have used these mouse stra ins in an i.v. model of Gram-negative sepsis to compare their sensitiv ities to infection, their cytokine responses, and the levels of induct ion of the enzyme nitric oxide synthase assayed in their livers. By us ing i.v. infection with Escherichia coli we have found that both strai ns are approximately equally sensitive to this organism, despite the C 3H/HeJ mice having a markedly attenuated TNF-alpha response. IFN-gamma levels after infection were identical in the two strains; the levels of nitric oxide synthase induced in their livers were about fourfold g reater in the C3H/HeJ mice. This difference could not be explained by differences in bacterial load. These experiments suggest that factors other than TNF-alpha are important in determining outcome from Gram-ne gative sepsis and that TNF-alpha is not a major factor in the inductio n of hepatic nitric oxide synthase after infection in vivo.