Will corticosteroids and other anti-inflammatory agents be effective for diarrhea-predominant irritable bowel syndrome?

Abstract

Irritable bowel syndrome (IBS) is one of several functional gastrointestinal disorders commonly encountered in both the clinical setting and the general population. The biopsychosocial model is currently believed to be a more complete explanatory mechanism of IBS symptom genesis and propagation. Gut inflammation and immune activation is one of the biological mechanisms for which evidence is emerging. Experimental parasitic infection of mice bowel resulted in elevated substance P levels and increased expression of cyclooxygenase 2 (COX 2) enzyme, prostaglandin E2, IL-4, IL-5, and IL-13. In IBS patients, increased cellularity and proximity of the inflammatory or immune cells to the nerve trunks of the bowel, elevated interleukin-1beta mRNA expression in mucosal biopsies, and increased inducible nitric oxide synthase and nitrotyrosine elaboration (indicative of lymphocyte activation) were observed. Corticosteroids given after the elimination of an experimentally applied parasite from the bowel of mice resulted in the reversal of persistent gut muscle dysfunction. Selective COX-2 inhibitors attenuated the increased bowel smooth muscle contractility resulting from parasite infection of mice gut. In humans, it has been observed that the relative risk of developing IBS in asthma patients was reduced by 60% by the use of oral steroids. Despite such preclinical and human evidence for the role of inflammation and immune activation in IBS, the efficacy of anti-inflammatory and immunomodulatory agents has not been adequately investigated. Budesonide, a corticosteroid with a high mucosal activity and a low bioavailability, is an anti-inflammatory agent that may be worth investigating for its utility in diarrhea-predominant IBS.

• Authors: Victor Crentsil
• Journal: Medical hypotheses (Med Hypotheses) Vol. 65 Issue 1 Pg. 97-102 ( 2005) ISSN: 0306-9877 [Print] United States
• PMID: 15893125 (Publication Type: Journal Article)

Chemical References

• Adrenal Cortex Hormones
• Anti-Inflammatory Agents
• Cytokines
• Membrane Proteins
• RNA, Messenger
• Substance P
• Budesonide
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Budesonide (therapeutic use)
• Cyclooxygenase 2
• Cytokines (metabolism)
• Diarrhea (complications)
• Dinoprostone (metabolism)
• Disease Models, Animal
• Humans
• Irritable Bowel Syndrome (drug therapy, etiology, parasitology)
• Lymphocyte Activation
• Membrane Proteins
• Mice
• Models, Biological
• Prostaglandin-Endoperoxide Synthases (metabolism)
• RNA, Messenger (metabolism)
• Substance P (metabolism)
• T-Lymphocytes (metabolism)
• Trichinella spiralis (parasitology)
• Trichinellosis