THE PRODUCTION OF EXPERIMENTAL CHOLECYSTITIS BY ENDOTOXIN

Acute acalculous cholecystitis (AAC) is a severe inflammatory disorder of the gallbladder. It occurs primarily in patients acutely ill from other disorders and is related to sepsis and shock. We previously foun d that platelet-activating factor (PAF), a phospholipid autacoid purpo rted to be a mediator of the shock response, produced AAC. This study was performed to determine the effect of intravenous lipopolysaccharid e (LPS) on feline gallbladders. Anesthetized cats underwent LPS admini stration with and without administration of a cyclooxygenase inhibitor and PAF antagonist. Gallbladder inflammation was evaluated by quantit ation of luminal water transport and tissue myeloperoxidase levels. In an attempt to understand the mechanisms of the response, gallbladder perfusate and tissue prostanoid and PAF levels were quantitated as wer e serum PAF levels. LPS administration resulted in alteration of the n ormal absorptive pattern of the gallbladder mucosa to exsorption of fl uid into the gallbladder lumen, increased tissue myeloperoxidase level s and increased serum PAF levels. This was associated with increased g allbladder tissue and perfusate prostanoid levels and increased perfus ate PAF levels. Indomethacin prevented the pro-inflammatory changes in the gallbladder produced by LPS. The PAF antagonist, alprazolam, incr eased gallbladder prostanoid production when administered alone and wi th LPS. The administration of LPS resulted in the production of acute changes in the gallbladder consistent with cholecystitis. These change s being prevented by a cyclooxygenase inhibitor suggests that developm ent of AAC may be related to the release of systemic and local pro-inf lammatory substances.