Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum

Gastroenterology. 2002 Aug;123(2):505-15. doi: 10.1053/gast.2002.34783.


Background & aims: Corticotropin-releasing hormone (CRH) released at local sites of inflammation promotes inflammation in the periphery. We investigated its effects in the intestinal responses caused by toxin A from Clostridium difficile, the causative agent of antibiotic-associated colitis.

Methods: Ileal loops were injected with 10 microg of toxin A, and enterotoxic responses were measured at various time points.

Results: Pretreatment of mice with 2.5 microg/kg of the CRH receptor antagonist alpha-helical CRH((9-41)) that blocks both CRH receptor subtypes reduced toxin A-mediated ileal secretion, epithelial cell damage, mucosal edema, neutrophil infiltration, and mucosal content of interleukin 1 beta and tumor necrosis factor alpha. Pretreatment with the specific CRH(1) receptor antagonist antalarmin (20 mg/kg, IP) also inhibited toxin A-induced fluid secretion and toxin A-associated histologic changes. CRH messenger RNA and protein were increased in mouse ileum 30 minutes after intraluminal toxin A administration. In situ hybridization and immunohistochemistry demonstrated that toxin A at 1 hour caused a substantial increase in the expression of both CRH receptor subtypes in the ileal mucosa.

Conclusions: Peripheral CRH may play a proinflammatory role in toxin A-induced intestinal secretion and inflammation and that CRH(1) receptor, at least in part, is important in the mediation of these responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bacterial Toxins / toxicity
  • Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / pharmacology*
  • Corticotropin-Releasing Hormone / physiology
  • Enteritis / drug therapy*
  • Enteritis / etiology
  • Hormone Antagonists / pharmacology*
  • Ileum / drug effects*
  • Ileum / metabolism
  • Male
  • Mice
  • Pyrimidines / pharmacology*
  • Pyrroles / pharmacology*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction


  • Anti-Inflammatory Agents
  • Bacterial Toxins
  • Hormone Antagonists
  • Pyrimidines
  • Pyrroles
  • RNA, Messenger
  • alpha helical corticotropin-releasing hormone
  • antalarmin
  • toxin A (Pseudomonas)
  • Corticotropin-Releasing Hormone