Pathogenesis of Clostridium perfringens infection: mechanisms and mediators of shock.

Abstract

Shock, a common complication of gas gangrene caused by Clostridium perfringens, is related to the elaboration of α- and θ-toxins in vivo. This study compared the relative potencies of θ- and α-toxins in a rabbit model and determined the role of endogenous mediators of toxin-induced shock. α-Toxin decreased cardiac index, mean arterial pressure, and heart rate and caused death in 83% of animals. θ-Toxin did not alter these parameters and caused death in only 25% of animals. α-Toxin also inhibited ex vivo cardiac contractility in a dose-dependent manner. Finally, both α-and θ-toxins were potent inducers of endothelial cell-derived platelet activating factor. α-Toxin, but not θ-toxin, also stimulated production of tumor necrosis factor by peripheral blood mononuclear cells. Thus, the fulminant nature of shock in patients with gas gangrene caused by C. perfringens is the sum of α-toxin's direct effects on myocardial contractility and both toxins' ability to induce production of potent endogenous mediators.