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

Akhtar S, Li X, Chaudry IH, Choudhry MA. Neutrophil chemokines and their role in IL-18-mediated increase in neutrophil O-2(-) production and intestinal edema following alcohol intoxication and burn injury. Am J Physiol Gastrointest Liver Physiol 297: G340-G347, 2009. First published June 4, 2009; doi: 10.1152/ajpgi.00044.2009.-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 (O-2(-)) and elastase following alcohol/ethanol (EtOH) and burn injury. Male rats (similar to 250 g) were gavaged with EtOH to achieve a blood EtOH level of similar to 100 mg/dl before similar to 12.5% total body surface area burn or sham injury. Immediately after injury, rats were administered with anti-rat IL-18 antibody (80 mu g/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 O-2-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.