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J Pharmacol Exp Ther. 1998 Oct;287(1):128-36.

Epithelial ion transport and barrier abnormalities evoked by superantigen-activated immune cells are inhibited by interleukin-10 but not interleukin-4.

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1
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada.

Abstract

Many studies have indicated an association between bacteria and the severity of enteric secretory or inflammatory disorders. We previously showed that monolayers of human T84 epithelial cells display altered ion transport and permeability after coculture with Staphylococcus aureus enterotoxin B (SEB, a model superantigen)-activated immune cells, where interferon-gamma and tumor necrosis factor-alpha were key mediators in the pathophysiology. Here we examined whether the regulatory Th2-type cytokines, interleukin (IL)-10 and IL-4, could prevent these epithelial irregularities. T84 monolayers were cocultured with human peripheral blood mononuclear cells (PBMC) or T cell-enriched, monocyte-depleted PBMC (T + B cells) +/- SEB for 20 hr in the presence or absence of IL-10 or IL-4. Subsequently, T84 monolayers were mounted in Ussing chambers and ion transport (short-circuit current (Isc) and DeltaIsc evoked by forskolin) and permeability (ion resistance and probe fluxes) were assessed. IL-10 dose-dependently inhibited the increased T84 permeability and the reduced responsiveness to forskolin that were evoked by coculture with SEB-activated PBMC or T + B cells. Similar changes in T84 function occurred in response to conditioned medium from SEB-activated immune cells; however, addition of IL-10 to the conditioned medium did not prevent the changes in epithelial function. In contrast, when PBMC were stimulated with SEB in the presence of IL-10, the subsequent conditioned medium was less effective in evoking altered epithelial function. These data suggest that the affect of IL-10 was due to effects on the immune cells and not directly on the epithelium. In contrast to IL-10, IL-4 did not ameliorate any of the immune-mediated changes in T84 function. We conclude that IL-10 can reduce the epithelial functional changes caused by SEB-activated immune cells and this data adds further support for IL-10 immunotherapy in the treatment of intestinal secretory or inflammatory disorders.

PMID:
9765331
[Indexed for MEDLINE]
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