Glucocorticoid Antagonism by Endotoxin: Biological Effects during Stress and Basis for Inhibition of Phosphoenolpyruvate Carboxykinase

摘要

Bacterial endotoxins produce a variety of pathophysiologic effects by inducing the release of humoral factors from cells of the reticuloendothelial system, primarily macrophages. This study focusses on one particular factor, glucocorticoid antagonizing factor (GAF). Antagonism was augmented when mice were subjected to conditions of stress where adrenoglucocorticoids are necessary for survival. Mice were sensitized to both toxic endotoxin and irradiated detoxified endotoxin during the stress of cold, heat, and tourniquet shock. Endotoxin, as well as detoxified endotoxin, induced the release of GAF from cells of the RES. Treatment of mice with this GAF-rich serum also resulted in their sensitization to stress. Survival of LPS-poisoned animals subjected to stress could be improved when exogenous hydrocortisone was given prior to the administration of exogenous GAF-rich serum or prior to the release of endogenous GAF in response to endotoxin. Naloxone, a B-endorphin antagonist, failed to increase the survival rate of animals under the experimental conditions investigated.