Reduction of Circulating Prostaglandin E sub 2 Level by Antiserum against Core Lipopolysaccharide in a Rabbit Model of Multiple Organ Failure

Objective: To determine the potential role of prostaglandin E₂ (PGE₂) in the development of multiple organ dysfunction or failure (MOF), the possible effects of antiserum directed against Re chemotype lipopolysaccharide (LPS, from Re mutant of Escherichia coli F515) on circulating PGE₂ level and survival rate, and whether there is an elevation in the plasma LPS concentration that could account for the induction of arachidonic acid metabolite in a rabbit model of MOF caused by acute hypovolemic insult.

Design, Materials, and Methods: An animal model of MOF in rabbits, engendered by feeding live Escherichia coli 0111:B4 before hemorrhagic shock (35-40 mm Hg for 60 min), was used in the present study. Re-LPS antiserum was given intravenously in the treatment group at the onset of hemorrhage and 4 hours after resuscitation. The animals that received equal volumes of normal rabbit serum and antiserum served as the control group.

Measurements and Main Results: The circulating PGE₂ level was not increased at the end of shock (p > 0.05), but it was found to be significantly elevated 24 hours after hemorrhage and resuscitation in both groups. However, Re-LPS antiserum administration markedly decreased peak PGE₂ level (p < 0.05) and attenuated multiple organ damage caused by acute insult. Concomitantly, there were also lower LPS concentrations in the treatment group as compared with the control group (p < 0.05-0.01). The survival rate was significantly increased in antiserum-treated rabbits 96 hours postinjury (treatment vs. control: 58.0% vs. 11.1%, p < 0.01).

Conclusions: The results suggest that an excessive generation and release of PGE₂ may be involved in the pathogenesis of immunosuppression and MOF following hemorrhage and resuscitation. Re-LPS antiserum has an inhibitory effect on overproduction of circulating PGE₂ and the ability to improve survival with MOF. Gut-derived endotoxemia, bacterial translocation, or both, could account, at least in part, for the PGE₂ formation and release in animals response to acute hypovolemic insult.