Characteristics of the intestinal epithelial barrier during dietary manipulation and glucocorticoid stress

Crit Care Med. 1996 Apr;24(4):635-41. doi: 10.1097/00003246-199604000-00015.

Abstract

Objectives: a) To determine the significance of stress-induced alterations in intestinal permeability by measuring the transmucosal flux of formyl-methionyl-leucyl-phenylalanine (f-MLP), a ubiquitous neutrophilic chemoattractant present in the human and rodent colon; and b) to determine whether stress and/or diet influence(s) bacterial adherence-induced changes in epithelial permeability by affecting the production of secretory immunoglobulin A (IgA), the main immune mechanism preventing bacterial adherence.

Design: Prospective, randomized, controlled study.

Setting: University animal research laboratory.

Subjects: Female Fischer rats.

Interventions: Rats were randomly assigned to four groups of seven animals each. Groups of animals were assigned to receive saline or dexamethasone (0.8 mg/kg ip) and were either starved (5% dextrose in water ad libitum) or fed (water and rat chow) for 48 hrs.

Measurements and main results: Mucosal barrier function was evaluated by measuring secretory IgA, bacterial adherence to the intestinal mucosa, and transepithelial electrical resistance, a measure of tight junction permeability. The f-MLP permeation across the mucosa was also determined in segments with significant permeability changes. Results indicate that starvation in dexamethasone-treated rats significantly impairs secretory IgA, promotes bacterial adherence to the mucosa, and results in increased intestinal permeability to f-MLP. These effects are significantly attenuated by the feeding of rat chow.

Conclusions: Alterations in intestinal barrier function are characterized by depressed IgA, bacterial adherence to the intestinal mucosa, and permeation of clinically relevant proinflammatory luminal macromolecules (f-MLP). Enteral stimulation with foodstuffs is a necessary protective measure to prevent altered epithelial barrier function during glucocorticoid stress.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Adhesion / physiology
  • Cell Membrane Permeability / physiology
  • Chemotactic Factors / pharmacokinetics
  • Dexamethasone / pharmacology*
  • Diet*
  • Epithelium / physiology
  • Female
  • Glucocorticoids / pharmacology*
  • Immunoglobulin A, Secretory / analysis
  • Intestinal Mucosa / physiology
  • Intestine, Large / physiology*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacokinetics
  • Prospective Studies
  • Random Allocation
  • Rats
  • Starvation / physiopathology
  • Stress, Physiological / physiopathology*

Substances

  • Chemotactic Factors
  • Glucocorticoids
  • Immunoglobulin A, Secretory
  • N-Formylmethionine Leucyl-Phenylalanine
  • Dexamethasone