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Vol. 287, Issue 1, 128-136, October 1998
Intestinal Disease Research Programme, McMaster University,
Hamilton, Ontario, Canada
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-
and tumor
necrosis factor-
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 
Isc 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.
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