Previous studies have shown that alcohol (EtOH) ingestion before
burn injury impaired intestinal barrier and immune function. This study determined whether EtOH and
burn injury up-regulate
interleukin (IL)-18 and whether
IL-18 up-regulation following EtOH and
burn injury is a cause for neutrophil recruitment and increased intestinal
edema. Rats (250 g) were gavaged with EtOH to achieve a blood EtOH level in the range of 100 mg/dL prior to
burn or
sham injury (25% total body surface area). A group of rats was treated with
Ac-YVAD-CHO (5 mg/kg), an inhibitor of caspase-1 (an
enzyme that converts pro-IL-18, an inactive form of IL-18, to mature IL-18), at the time of injury. One day after injury, rats were killed.
IL-18 production was determined in circulation and in the supernatants harvested from spleen, mesenteric lymph nodes, and Peyer's patch cell cultures as well as in intestinal tissue homogenates. Neutrophil accumulation in intestine was determined by measuring
myeloperoxidase (MPO) activity. We found a significant increase in
IL-18 levels in the lymphoid cell supernatants and intestinal tissue homogenates obtained from EtOH and
burn-injured rats compared with the rats receiving
burn or
sham injury. This was accompanied by an increase in intestinal MPO and
edema. No demonstrable change in intestinal morphology was observed in any group. Treatment of rats with
caspase-1 inhibitor significantly attenuated the increase in
IL-18 levels and intestinal MPO activity in EtOH and
burn-injured rats. Inhibition of
IL-18 also prevented an increase in intestinal tissue water content. As MPO is considered an index of neutrophil infiltration, results presented in this manuscript collectively suggest that
IL-18 up-regulation is likely to contribute to the increased neutrophil infiltration and
edema in intestinal tissue observed following EtOH and
burn injury.