A monoclonal antibody against cytokine-induced neutrophil chemoattractant attenuates injury in the small intestine in a model of ruptured abdominal aortic aneurysm.

Abstract

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. 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. 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. 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.