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Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G340-7. doi: 10.1152/ajpgi.00044.2009. Epub 2009 Jun 4.

Neutrophil chemokines and their role in IL-18-mediated increase in neutrophil O2- production and intestinal edema following alcohol intoxication and burn injury.

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Burn and Shock Trauma Institute and Alcohol Research Program, Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.


We examined the role of interleukin (IL)-18 and cytokine-induced neutrophil chemokines (CINC)-1 and CINC-3 in the neutrophil release of superoxide anion (O2-) and elastase following alcohol/ethanol (EtOH) and burn injury. Male rats (approximately 250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dl before approximately 12.5% total body surface area burn or sham injury. Immediately after injury, rats were administered with anti-rat IL-18 antibody (80 microg/kg) or isotype control. After 20 min, anti-IL-18 antibody-treated rats were given either recombinant (r) rat CINC-1 or CINC-3. On day 1 after injury, the combined insult of EtOH and burn injury caused a significant increase in neutrophil elastase and O2- production as well as an increase in neutrophil accumulation, myeloperoxidase activity, and edema in the intestine. Treatment of rats with anti-IL-18 antibody normalized the above parameters. However, administration of rCINC-1 in anti-IL-18 antibody-treated rats increased the above parameters to levels similar to those observed following EtOH and burn injury. In contrast, administration of rCINC-3 did not influence the above parameters except neutrophil elastase. These findings indicate that IL-18 and CINC-1 may independently modulate neutrophil tissue-damaging actions following EtOH and burn injury. However, the finding that the treatment of rats with anti-IL-18 antibodies inhibits CINC-1 and CINC-3 supports the notion that IL-18 plays a critical role in increased neutrophil tissue-damaging action following a combined insult of EtOH intoxication and burn injury.

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