Monokines and the metabolic pathophysiology of septic shock

The role of the macrophage system in shock pathogenesis now embraces both classic endocytic functions as well as the more recently discovered function of the macrophages as a multifaceted secretory apparatus. Among the major macrophage secretory products are the monokines, regulatory proteins that mediate via both local or paracrine and systemic or endocrine mechanisms, the nonspecific host defense and metabolic responses to inflammation and sepsis. Evidence is reviewed for a monokine involvement in the alterations of protein, fat, and carbohydrate metabolism in sepsis and/or endotoxicosis, viz., enhanced muscle proteolysis, enhanced hepatic acute phase protein synthesis, depressed lipogenesis and lipoprotein lipase function, enhanced peripheral glucose oxidation, and depression of hepatic gluconeogenesis. Monokines are also related to the disturbed endocrine mechanisms of sepsis, viz., enhanced insulin secretion and depressed adrenal steroidogenesis. It is suggested that the macrophage system mediates via secretion of monokines an integrated fuel substrate and hormonal adjustment to sepsis, which on the one hand may provide optimal metabolic homeostasis for systemic host defense, but on the other hand, if allowed to act unchecked, may contribute to the metabolic dyshomeostasis of septic shock.