LPS pretreatment protects from hepatic ischemia/reperfusion.

In vivo administration of nonlethal doses of lipopolysaccharide (LPS) to rodents can result in protection from subsequent lethal doses of endotoxin or LPS. We have previously demonstrated that hepatic ischemia/reperfusion (I/R) results in a TNF-dependent lung and liver injury and we postulated that pretreatment with sublethal concentrations of LPS prior to hepatic I/R could be protective from this injury. To test this hypothesis, five groups of rats were studied. LPS-I/R received 25 micrograms of LPS i.v. 24 hr prior to I/R, VEH-I/R received an equivalent volume of vehicle iv 24 hr prior to I/R, LPS-LPS received 25 micrograms of LPS i.v. 24 hr prior to sham laparotomy at which time an additional 25 micrograms of LPS was given i.v., VEH-LPS received an equivalent volume of vehicle 24 hr prior to sham laparotomy and 25 micrograms of LPS i.v. immediately prior to sham laparotomy, and SHAM consisted of sham-operated control animals. Peak plasma tumor necrosis factor-alpha (TNF) levels occurred between 30 and 150 min of reperfusion: LPS-I/R = 778 +/- 150 pg/ml (n = 5), VEH-I/R = 145 +/- 46 pg/ml (n = 5), LPS-LPS = 970 +/- 716 pg/ml (n = 4), VEH-LPS = 15,949 +/- 10,937 (n = 5), and SHAM = 3 +/- 1 (n = 5). As previously demonstrated by other investigators, pretreatment with LPS decreases TNF release in response to a second dose of LPS; however, TNF release was increased following hepatic I/R in those animals pretreated with LPS (LPS-I/R vs VEH-I/R, P = 0.014).(ABSTRACT TRUNCATED AT 250 WORDS)