Endotoxins, arachidonic acid, and superoxide formation.

The pathophysiologic relevance of altered eicosanoid metabolism and free-radical production during endotoxemia is reviewed. A direct or complement-mediated release of eicosanoids--depending on the species, the tissue, and the kind of endotoxin--has been found to be associated with endotoxemic shock. Prostacyclin appears to be partially responsible for the early decrease in blood pressure and clearly induces the sustained hypotension of endotoxemia but is irrelevant to its fatal outcome. In contrast, simultaneous administration of vasodilating prostanoids such as prostaglandin E1 and metabolically stable analogues of prostacyclin prevents endotoxin lethality. Thromboxane A2 may contribute to platelet aggregation and vasoconstriction, but its quantitative importance often is obscured by other mediators. The peptidoleukotrienes, in particular leukotriene D4, contribute to lung damage and--in galactosamine-sensitized rats, at least--to fatal liver destruction. Little is known about the role of leukotriene B4 in endotoxemia. Endotoxin suppresses rather than stimulates superoxide release from phagocytes in vitro but leads to massive free-radical formation mediated by complement activation in vivo and, thereby, contributes to lung injury.