title: A monoclonal antibody against cytokine-induced neutrophil chemoattractant attenuates injury in the small intestine in a model of ruptured abdominal aortic aneurysm.
abstract: OBJECTIVE
  Ruptured abdominal aortic aneurysm (RAAA) continues to be a major source of aneurysm-related morbidity and mortality. Neutrophils have been implicated in RAAA repair-induced organ injury; however, the agents responsible for neutrophil activation and organ sequestration have not been identified. This study investigated the role of cytokine-induced neutrophil chemoattractant (CINC) in organ injury in an RAAA model.
  
  
  METHODS
  Rats were subjected to 1 hour of hemorrhagic shock with resuscitation, followed by 45 minutes of lower torso ischemia and 2 hours of reperfusion, and randomly were selected to receive saline solution or anti-rat CINC monoclonal antibody at the start of hemorrhagic shock. Another group of animals underwent sham operation, and served as a control group. Intestinal and lung permeability, intestinal and lung myeloperoxidase (MPO) activity, intestinal and lung CINC, and tumor necrosis factor-alpha (TNF-alpha) levels, resuscitation fluid requirements, and histologic mucosal injury were evaluated in all groups.
  
  
  RESULTS
  The RAAA model resulted in increased lung and intestinal permeability to radiolabeled albumin and lung MPO activity (P <.01), with increases in intestinal TNF-alpha (P <.001) and CINC (P <.01) levels, when compared with sham-operated animals. Treatment with anti-rat CINC monoclonal antibody attenuated the increases in intestinal permeability and histologic mucosal injury (P <.01), gut TNF-alpha level (P <.001), and resuscitation fluid volume required (P <.05), without significantly affecting lung and intestinal MPO activity, lung permeability, and intestinal CINC level (P = NS), compared with animals given saline solution.
  
  
  CONCLUSIONS
  Neutralization of CINC by the anti-rat CINC monoclonal antibody attenuated intestinal injury and induction of intestinal TNF-alpha, but failed to significantly attenuate remote pulmonary injury in this model of RAAA.
authors.affiliation: Division of Vascular Surgery, Toronto General Hospital, and the Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ebenezar M
authors.initials: EM
authors.lastname: Mbachu
authors.forename: Lazar V
authors.initials: LV
authors.lastname: Klein
authors.forename: Barry B
authors.initials: BB
authors.lastname: Rubin
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lindsay
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology*; D001019:Aortic Rupture / Q000473:pathology*; D019743:Chemokines, CXC / Q000276:immunology* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology* / Q000494:pharmacology; D007421:Intestine, Small / Q000473:pathology*; D008168:Lung / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control; D012771:Shock, Hemorrhagic / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins