Endogenous corticosteroids modulate Clostridium difficile toxin A-induced enteritis in rats.

Abstract

We examined the role of glucocorticoids in acute inflammatory diarrhea mediated by Clostridium difficile toxin A. Toxin A (5 microg) or buffer was injected in rat ileal loops, and intestinal responses were measured after 30 min to 4 h. Ileal toxin A administration increased plasma glucocorticoids after 1 h, at which time the toxin-stimulated secretion was not significant. Administration of the glucocorticoid analog dexamethasone inhibited toxin A-induced intestinal secretion and inflammation and downregulated toxin A-mediated increase of macrophage inflammatory protein-2. Adrenalectomy followed by replacement with glucocorticoids at various doses suggested that intestinal responses to toxin A were related to circulating levels of glucocorticoids. Administration of the glucocorticoid receptor antagonist RU-486 enhanced toxin A-mediated intestinal secretion and inflammation. We conclude that C. difficile toxin A causes increased secretion of endogenous glucocorticoids, which diminish the intestinal secretory and inflammatory effects of toxin A.

• Authors: I Castagliuolo, K Karalis, L Valenick, A Pasha, S Nikulasson, M Wlk, C Pothoulakis
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 280 Issue 4 Pg. G539-45 (Apr 2001) ISSN: 0193-1857 [Print] United States
• PMID: 11254479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents
• Bacterial Toxins
• Chemokine CXCL2
• Chemotactic Factors
• Enterotoxins
• Glucocorticoids
• Hormone Antagonists
• Monokines
• tcdA protein, Clostridium difficile
• Mifepristone
• Dexamethasone

Topics

• Adrenalectomy
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bacterial Toxins (antagonists & inhibitors, toxicity)
• Chemokine CXCL2
• Chemotactic Factors (biosynthesis)
• Dexamethasone (pharmacology)
• Enteritis (chemically induced, prevention & control)
• Enterotoxins (antagonists & inhibitors, toxicity)
• Glucocorticoids (pharmacology)
• Hormone Antagonists (pharmacology)
• Ileum (drug effects)
• Intestinal Mucosa (cytology, drug effects)
• Male
• Mifepristone (pharmacology)
• Monokines (biosynthesis)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation (drug effects)