ON THE MECHANISM OF PROTECTION OF ENDOTOXIN SHOCK BY GLUCOCORTICOIDS.

Abstract

It was shown that the extreme susceptibility to endotoxin after adrenalectomy in dogs seemed to be due to the intensification of hepatic responses to endotoxin. A complete depletion of liver glycogen together with a release of an endogenous “shock-inducing factor” was induced in the absence of glucocorticoids. This factor could be detected by passive transfer of the plasma of endotoxin-shocked adrenalectomized dogs. By inducing a hepatosplanchnic blood pooling it mainly determined the severity of the shock. It was non-dializable and heat-unstable. Glucocorticoid could prevent its release from the liver together with the glycogen depletion, but could not inhibit its action. Thus the mechanism of protection of endotoxin shock by glucocorticoid in adrenalectomized dogs was found to be due to the prevention of the induction of the hepatic responses. Once the responses were started it was hardly possible to check them by glucocorticoid. Thus the timing of the glucocorticoid administration was of prime importance in preventing the endotoxin shock. It was discussed that the prevention of liver glycogen depletion in response to endotoxin by glucocorticoid was not due to its so-called gluconeogenesis.