Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model

Cirle Alcantara, William F. Stenson, Theodore S. Steiner, Richard L. Guerrant

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Cyclooxygenase (Cox)-2 expression and inhibition were investigated in a rabbit ileal loop model of Clostridium difficile colitis and diarrhea. Intestinal tissue stimulated with C. difficile toxin A showed up-regulation of Cox-2 expression in lamina propria macrophages and elevated prostaglandin levels. Toxin A-stimulated loops exhibited severe inflammation and increased secretory volume. Celecoxib, a specific Cox-2 inhibitor, significantly reduced toxin A-induced prostaglandin production. Furthermore, celecoxib (0.02 mg/mL) blocked both histologic damage (mean histologic grade, 1.25 vs. 3.44 in rabbits receiving toxin A alone; P < .0005) and secretion (volume:length ratio, 0.18 vs. 0.72 in those receiving toxin A alone; P = .002) in toxin A-stimulated loops in a dose-related manner. Thus, toxin A induced expression of Cox-2 in the host, and prostaglandins produced through Cox-2 were involved in the mediation of the increased secretion of electrolytes and water and the inflammatory response induced by toxin A.

Original languageEnglish
Pages (from-to)648-652
Number of pages5
JournalJournal of Infectious Diseases
Volume184
Issue number5
DOIs
StatePublished - Sep 2001

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