Submitted on February 4, 2009
Revised on April 30, 2009
Accepted on May 30, 2009
Neutrophil chemokines and their role in IL-18-mediated increase in neutrophil O2- production and intestinal edema following alcohol intoxication and burn injury
Suhail Akhtar1, Xiaoling Li1, Irshad H. Chaudry2, and Mashkoor A Choudhry3*
1 Loyola University Medical Center
2 U Alabama at Birmingham
3 Loyola University Chicago Medical Center
* To whom correspondence should be addressed. E-mail: mchoudhry{at}lumc.edu.
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 (~250 g) were gavaged with EtOH to achieve a blood EtOH level of ~100 mg/dL prior to 12.5% total body surface area burn or sham burn. Immediately after injury, rats were administered with anti-rat IL-18 antibody (80 µg/kg) or isotype control. After 20 min, anti-IL-18 antibody-treated rats were given either recombinant rat CINC-1 or CINC-3. On day one 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 (MPO) activity and edema in the intestine. Treatment of rats with anti-IL-18 antibody normalized the above parameters. However, administration of CINC-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 CINC-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.
