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Glucocorticoid resistance in inflammatory bowel disease
1Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. rfarrell@bidmc.harvard.edu
The Journal of Endocrinology
|September 12, 2003
Summary
Glucocorticoid resistance in inflammatory bowel disease (IBD) is poorly understood. Key mechanisms involve drug efflux, receptor dysfunction, and impaired signaling, impacting treatment effectiveness for Crohn's disease and ulcerative colitis.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Glucocorticoids are effective for inflammatory bowel disease (IBD) but treatment resistance is common.
- Resistance necessitates surgery in up to 50% of Crohn's disease (CD) and 20% of ulcerative colitis (UC) patients.
- Understanding glucocorticoid resistance pathophysiology in IBD is crucial.
Purpose of the Study:
- To review the molecular mechanisms of glucocorticoid resistance in IBD.
- To discuss the impact of disease heterogeneity and pharmacogenetics on glucocorticoid responsiveness.
Main Methods:
- Literature review focusing on molecular mechanisms of glucocorticoid resistance in IBD.
- Analysis of studies on T-lymphocyte and inflammatory cell resistance.
- Discussion of multidrug resistance gene (MDR1), glucocorticoid receptor (GR) function, and nuclear factor kappa B (NF-κB) pathways.
Main Results:
- Three key mechanisms identified: increased drug efflux via MDR1, impaired glucocorticoid receptor signaling, and constitutive epithelial activation inhibiting GR activity.
- Glucocorticoid resistance is compartmentalized to T-lymphocytes and other inflammatory cells.
- Disease heterogeneity and pharmacogenetics influence glucocorticoid responsiveness.
Conclusions:
- Molecular mechanisms underlying glucocorticoid resistance in IBD are complex and multifactorial.
- Further research into these mechanisms may lead to improved therapeutic strategies for IBD.
- Understanding pharmacogenetics can personalize glucocorticoid treatment for IBD patients.
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