Inhibition of complement C5 reduces local and remote organ injury after intestinal ischemia/reperfusion in the rat

Background & Aims: Complement activation plays an important role in the loc al pathogenesis of ischemia/reperfusion (I/R) injury. We investigated the a ction of anti-C5 monoclonal antibody (mAb) on local and remote organ injuri es after intestinal I/R in the rat. Methods: Under anesthesia, functional a nti-rat C5 mAb (18A), an isotype-matched control anti-C5 mAb (16C), or vehi cle (phosphate-buffered saline) was administered 60 minutes before the supe rior mesenteric artery was occluded for 90 minutes and reperfused for 60 mi nutes. Tissue injury was assessed by lactate dehydrogenase release, myelope roxidase activity, and microvessel relaxation. Tumor necrosis factor (TNF)- alpha, interleukin (IL)-1 alpha, and intercellular adhesion molecule (ICAM) -1 expression was assessed by reverse-transcription polymerase chain reacti on and immunohistochemistry. Results: The loss of endothelium-dependent rel axation of microvessels from the superior mesenteric artery after I/R was s ignificantly attenuated by 18A but not by 16C. Intestinal lactate dehydroge nase release after I/R was significantly reversed by 18A treatment. Anti-C5 treatment significantly inhibited the increased myeloperoxidase activity i n the lung and intestine after intestinal I/R. Furthermore, increased intes tinal TNF-alpha, IL-1 alpha, and vascular ICAM-1 expression after I/R were significantly inhibited by anti-C5 mAb. Conclusions: Anti-C5 therapy signif icantly improved intestinal I/R tissue injury as well as lung injury.