Is exposure to bacterial endotoxin a determinant of susceptibility to intoxication from xenobiotic agents?
Why certain individuals are more susceptible than others to harmful effects of chemical exposure remains incompletely understood. One understudied but potentially important determinant of susceptibility is concurrent or preexisting inflammation that may influence the pathogenic outcome of chemical exposure. Endotoxin from gram-negative bacteria is a potent inducer of inflammation. We are all exposed to endotoxin, and such exposure varies considerably among individuals depending on environment, bacterial infection, and conditions that affect its translocation from the lumen of the gastrointestinal tract into the circulation. Mammals have a vigorous response to endotoxin that includes recruitment and activation of inflammatory cells and release of many soluble mediators that affect cellular homeostasis. These and other results have led to the hypothesis that altered tissue homeostasis initiated by small, otherwise nontoxic doses of xenobiotic agents can progress to overt toxicity in the
