Effect of lead acetate on the susceptibility of rats to bacterial endotoxins.

Selye, H. (Université de Montréal, Montreal, Canada), B. Tuchweber, and L. Bertók. Effect of lead acetate on susceptibility of rats to bacterial endotoxins. J. Bacteriol. 91:884-890. 1966.-A single, normally well-tolerated, intravenous injection of lead acetate increases the sensitivity of the rat to the endotoxins of various gram-negative bacteria about 100,000 times above normal. Under the conditions of these experiments, the mortality and organ changes normally produced by the intravenous injection of 100 mug of Escherichia coli endotoxin were essentially the same as those obtained by use of 1 nanogram in lead-sensitized rats. The sensitizing effect of lead acetate for E. coli endotoxin is greatest when the two agents are given simultaneously. However, considerable sensitization is still detectable when endotoxin is injected up to 1 hr before or 7 hr after sensitization with lead. No sensitization was noted when the endotoxin was administered 24 hr before or after lead acetate. Under our experimental conditions, the minimal dose of lead acetate which could still induce significant sensitization to E. coli endotoxin was 1 mg per 100 g of body weight. Although lead acetate induces a high degree of susceptibility to various endotoxins, other reticuloendothelial blocking agents did not acquire unusual toxicity after pretreatment with lead. Finally, none of the other metals or reticuloendothelial blocking agents tested could duplicate the pronounced decrease in endotoxin resistance induced by lead acetate.