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Molecular Medicine

, Volume 17, Issue 1–2, pp 88–94 | Cite as

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

  • Suhail Akhtar
  • Xiaoling Li
  • Elizabeth J. Kovacs
  • Richard L. Gamelli
  • Mashkoor A. Choudhry
Research Article

Abstract

Studies have shown that burn patients who are intoxicated at the time of injury are more susceptible to infection and have a higher incidence of mortality. A major cause of death in burn and trauma patients regardless of their alcohol (EtOH) exposure is multiple organ dysfunction, which is driven in part by the systemic inflammatory response and activated neutrophils. Neutrophils are short lived and undergo apoptosis to maintain homeostasis and resolution of inflammation. A delay in apoptosis of neutrophils is one important mechanism which allows for their prolonged presence and the release of potentially harmful enzymes. The purpose of this study was to examine whether EtOH intoxication combined with burn injury influences neutrophil apoptosis and whether IL-18 plays any role in this setting. To accomplish this investigation, rats were gavaged with EtOH (3.2 g/kg) 4 h before being subjected to sham or burn injury of ~12.5% of the total body surface area, and then killed on d 1 after injury. Peripheral blood neutrophils were isolated and lysed. The lysates were analyzed for pro-and antiapoptotic proteins. We found that EtOH combined with burn injury prolonged neutrophil survival. This prolonged neutrophil survival was accompanied by a decrease in the levels of the neutrophil proapoptotic protein Bax, and an increase in antiapoptotic proteins Mcl-1 and Bcl-xl. Administration of IL-18 antibody following burn injury normalized the levels of Bax, Mcl-1 and Bcl-xl. The decrease in caspase-3 and DNA fragmentation observed following EtOH and burn injury was also normalized in rats treated with anti-IL-18 antibody. These findings suggest that IL-18 delays neutrophil apoptosis following EtOH and burn injury by modulating the pro-and antiapoptotic proteins.

Notes

Acknowledgments

This study was supported by the National Institutes of Health through R01AA015731 and R21AA015979.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Suhail Akhtar
    • 1
    • 3
    • 4
  • Xiaoling Li
    • 1
    • 3
    • 4
  • Elizabeth J. Kovacs
    • 1
    • 2
    • 3
    • 4
  • Richard L. Gamelli
    • 1
    • 3
    • 4
  • Mashkoor A. Choudhry
    • 1
    • 2
    • 3
    • 4
  1. 1.Departments of SurgeryLoyola University Chicago Medical CenterMaywoodUSA
  2. 2.Departments of Microbiology and ImmunologyLoyola University Chicago Medical CenterMaywoodUSA
  3. 3.Departments of Alcohol Research ProgramLoyola University Chicago Medical CenterMaywoodUSA
  4. 4.Burn and Shock Trauma Institute, Bldg, 110/EMS; Room 4236Loyola University Chicago Medical CenterMaywoodUSA

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