Modulation of intestinal barrier function by glucocorticoids: Lessons from preclinical models

Area of Science:

• Gastroenterology
• Pharmacology
• Immunology

Background:

• Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant drugs.
• Adverse effects of GCs are well-documented, but their impact on intestinal barrier function is less understood.
• Intestinal barrier integrity is crucial for maintaining gut homeostasis and preventing systemic inflammation.

Purpose of the Study:

• To review and summarize existing studies on the effects of GCs on intestinal barrier function.
• To explore the variable effects of GCs in different experimental models and conditions.
• To discuss the potential mechanisms underlying GC-mediated alterations in gut barrier integrity.

Main Methods:

• Review of published literature on GCs and intestinal barrier function.
• Analysis of studies conducted in cultured intestinal epithelial cells.
• Analysis of studies conducted in animal models (rodents and other animals).

Main Results:

• In cultured cells, GCs show variable effects, often enhancing barrier function with inflammatory cytokines like TNF.
• In animal models, GCs can weaken barrier function, increasing permeability and reducing IgA production.
• GCs demonstrate context-dependent effects in experimental colitis and sepsis models, sometimes enhancing barrier function.

Conclusions:

• Glucocorticoids exert complex and context-dependent effects on intestinal barrier function.
• Mechanisms include modulation of epithelial cell proliferation, wound healing, microbiota, mucus, and mucosal immunity.
• Further research is needed to fully elucidate GC-mediated effects on the gut barrier in various disease states.