Neutrophil chemokines and their role in IL-18-mediated increase in neutrophil O2- production and intestinal edema following alcohol intoxication and burn injury.
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.
Akhtar
Suhail
S
Burn and Shock Trauma Institute and Alcohol Research Program, Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Li
Xiaoling
X
Chaudry
Irshad H
IH
Choudhry
Mashkoor A
MA
D000435:Alcoholic Intoxication / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002056:Burns / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054360:Chemokine CXCL1 / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism*; D007410:Intestinal Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D000906:Antibodies; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D020382:Interleukin-18; D011994:Recombinant Proteins; D013481:Superoxides; D019272:Leukocyte Elastase