The nonresponder C3H HeJ mouse was nearly 50-fold more sensitive than the C3H eb parent to the lethal effects of bacterial endotoxins. Just 1 mg triamcinolone acetonide (TA) protected against 5 mg bacterial lipopolysaccharide (LPS) that produced 40% lethality in the C3H HeJ strain. The nonresponder mice were sensitized to endotoxin lethality by either glucan or streptozotocin (SZN) and the combined effect of these two materials was clearly additive; TA again protected against LPS under these coditions. The degree of sensitization to LPS by either agent was greater in the C3H HeJ strain as compared to both the parent C3H eb mice and the OF1 Swiss albino animals. Glucan increased all parameters of the reticuloendothelial system (RES) equally well in all strains of mice. TA protection against LPS was associated with an actual decrease in reticuloendothelial activity under these conditions; SZN did not influence the RES at all. Although LPS lowered glycemia within the first 4 hr, SZN, TA, or glucan had no effect on this parameter. The influence of TA and LPS on liver glycogen was similar in the nonresponder and the responder mice. Liver glucocorticoid receptor levels, too, were nearly identical in both strains. It is suggested that the classical lps gene hypothesis may not suffice to explain the mechanism of nonresponsiveness to endotoxins in C3H HeJ mice which, contrary to earlier observations, can be rendered nearly as responsive as conventional mice. Furthermore, streptozotocin would seem to have extrapancreatic sites of action that we had suggested in earlier studies.
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