Induction of early-phase tolerance to endotoxin-induced mucosal injury, xanthine oxidase activation, and bacterial translocation by pretreatment with endotoxin.

The goal of this study was to determine whether tolerance would develop to endotoxin-induced mucosal injury, xanthine oxidase activation, and bacterial translocation. To accomplish this goal, four groups of mice were studied: 1) mice receiving ip injections of saline 96 and 24 hr prior to sacrifice, 2) mice receiving ip injections of saline 96 and endotoxin (0.1 mg) 24 hr prior to sacrifice, 3) mice receiving ip injections of endotoxin 96 and 24 hr prior to sacrifice, and 4) mice receiving ip injections of endotoxin 96 hr and saline 24 hr prior to sacrifice. In contrast to the saline control animals or mice sacrificed 96 hr after a single dose of endotoxin, mice sacrificed 24 hr after receiving a single dose of endotoxin had evidence of mucosal injury, elevated levels of ileal xanthine oxidase activity, and an 81% incidence of bacterial translocation. Mice sacrificed 24 hr after a second dose of endotoxin were largely protected against the toxic effects of endotoxin. Thus tolerance to endotoxin-induced bacterial translocation does develop and is associated with tolerance to endotoxin-induced ileal mucosal injury and xanthine oxidase activation.