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

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Abstract

Purpose: 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-α (TNF-α) 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-α (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-α 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. Conclusion: Neutralization of CINC by the anti-rat CINC monoclonal antibody attenuated intestinal injury and induction of intestinal TNF-a, but failed to significantly attenuate remote pulmonary injury in this model of RAAA.

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Mbachu, E. M., Klein, L. V., Rubin, B. B., & Lindsay, T. F. (2004). A monoclonal antibody against cytokine-induced neutrophil chemoattractant attenuates injury in the small intestine in a model of ruptured abdominal aortic aneurysm. Journal of Vascular Surgery, 39(5), 1104–1111. https://doi.org/10.1016/j.jvs.2004.01.017

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