Tolerance and sensitization to endotoxin

Experimental animals receiving minute amounts of endotoxin may become tolerant to a subsequent challenge with pyrogenic or lethal amounts of endotoxin. In humans an initial pyrogenic dose of endotoxin induces tolerance to the pyrogenic effect of subsequent endotoxin challenges carried out within short intervals (less than 10 days).

In contrast, normal sensitivity to endotoxin may be increased by treatment with live or killed gram-negative and -positive bacteria. Examples of these arc BCG, Propionibacterium acnes, Coxiella burnetii and Salmonella typhimurium. Interferon y (IFNy) is an important mediator of the bacteria-induced sensitization to endotoxin. Sensitization to endotoxin is also induced by parasitic and viral infections. Also, hepatoxic agents, such as D-galactosamine and a-amanitin, and various chemical agents, including actinomycin D, lead acetate and carbon tetrachloride enhance endotoxin activity. In addition, growing tumors, depletion of cortisone (in mice) by adrenalectomy or acute graft-versus-host reaction will lead to a higher sensitivity towards endotoxin.

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