16-16-dimethylprostaglandin-e and Escherichia-coli-Infections

The immunosuppression seen following burn injury has frequently been attributed to elevated prostaglandin E levels. We evaluated the contribution of elevated prostaglandin E levels on susceptibility to infectious complications utilizing multiple mouse models. The administration of 100 micrograms/kg of the long-acting derivative of prostaglandin E, 16,16-dimethyl-prostaglandin E, was found to improve survival in C3/HEN mice challenged with 1 x 10(8) Escherichia coli organisms intraperitoneally. The administration of indomethacin was found to decrease survival in the same model. With C3/HEJ (endotoxin-resistant) mice, indomethacin was found to increase mortality rates in animals challenged with 1 x 10(8), 1 x 10(9) or 1 x 10(10) Escherichia coli organisms. These findings suggest that elevated prostaglandin E levels seen in burn patients may not be responsible for the postburn increased susceptibility to infectious complications.

Topics: Animals; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Immune Tolerance; Indomethacin; Male; Mice; Mice, Inbred C3H; Prostaglandins E, Synthetic; Random Allocation

Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE-treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001).

Topics: Animals; Escherichia coli Infections; Male; Peritonitis; Prostaglandins E, Synthetic; Rats; Rats, Inbred Lew; Shock, Septic; Tumor Necrosis Factor-alpha