Sepsis and other
critical illnesses are associated with increased permeability of the intestinal mucosa. Loss of mucosal integrity may lead to
multiple organ failure in these conditions. We tested the hypothesis that induction of the heat shock response reduces
sepsis-induced increase in intestinal permeability. The heat shock response was induced in mice by
intraperitoneal injection of 10 mg/kg
sodium arsenite. Two hours later, at which time mucosal
heat shock protein 72 levels were increased,
sepsis was induced by cecal
ligation and
puncture (CLP) or
sham operation was performed. Sixteen hours after
sham operation or CLP, intestinal permeability was determined by measuring the appearance in blood of 4.4-kDa
fluorescein isothiocyanate-conjugated
dextran and 40-kDa
horseradish peroxidase administered by gavage.
Sepsis resulted in increased mucosal permeability for both markers, and this effect of
sepsis was substantially reduced in mice treated with
sodium arsenite. Plasma levels of the anti-inflammatory
cytokine interleukin (IL)-10 were increased in septic mice pretreated with
sodium arsenite, and the protective effect of
sodium arsenite on intestinal permeability in septic mice was reversed by treatment with anti-IL-10 antibody. The present results suggest that
sepsis-induced increase in mucosal permeability can be reduced by the heat shock response and that increased
IL-10 levels may be involved in the protective effects of the heat shock response.