The role of leukotriene B4 in Clostridium difficile toxin A-induced ileitis in rats.


Journal Article

BACKGROUND & AIMS: Clostridium difficile toxin A is a potent intestinal inflammatory agent that has been shown to act at least partially by neurogenic mechanisms involving activation of the transient receptor potential vanilloid 1 (TRPV1) (capsaicin) receptor. We tested the hypothesis that leukotriene B4 (LTB4) mediates the effects of toxin A via activation of the TRPV1 receptor. METHODS: Isolated rat ileal segments were pretreated with pharmacologic agents before intraluminal injection of toxin A or LTB4. After 3 hours, the treated segments were removed and inflammation was assessed by luminal fluid accumulation, myeloperoxidase activity, and histology. RESULTS: LTB4 caused ileitis similar to that caused by toxin A and antagonism of TRPV1 receptors but not LTB4 receptors inhibited LTB4-induced inflammation. LTB4 also stimulated TRPV1-mediated substance P release and pretreatment with a specific substance P-receptor antagonist blocked LTB4-induced substance P action and ileitis. Inhibition of the LTB4 biosynthetic enzyme 5-lipoxygenase inhibited toxin A-induced increases in ileal LTB4 levels and toxin A- but not LTB4-induced ileitis. CONCLUSIONS: LTB4 mediates the inflammatory effects of toxin A via activation of TRPV1 receptors.

Full Text

Duke Authors

Cited Authors

  • McVey, DC; Vigna, SR

Published Date

  • May 2005

Published In

Volume / Issue

  • 128 / 5

Start / End Page

  • 1306 - 1316

PubMed ID

  • 15887113

Pubmed Central ID

  • 15887113

International Standard Serial Number (ISSN)

  • 0016-5085

Digital Object Identifier (DOI)

  • 10.1053/j.gastro.2005.03.017


  • eng

Conference Location

  • United States