Mechanisms of action

The mechanisms by which endotoxin exerts its toxic activities remained unknown up to the middle of the 1980s. Today it is generally agreed that the biological activities of endotoxin are caused indirectly through the action of endogenous mediators induced after interaction of endotoxin with primary targets. Macrophages are probably the most important targets of endotoxin, playing a central position in the development of endotoxicity. Following interaction with endotoxin, macrophages are activated to produce a number of cytokines, such as tumor necrosis factor a (TNFa) and various interleukins (ILs). TNFa is a primary mediator of the lethal activity of endotoxin. Exogenous TNFa administered into experimental animals induces a lethal shock that is indistinguishable from that induced by endotoxin. In certain experimental models antibodies to TNFa inhibit the development of endotoxin shock.

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