The Effect of CD18 Monoclonal Antibody on Tissue and Serum Interleukin-8 Concentration in Reperfusion Injury

ABSTRACT

It remains a problem that successful revascularization and reperfusion after ischemia are associated with high systemic complication rates and severe local tissue injuries. With prolonged ischemia, there is damage to tissue from anoxia, but further injury may occur after reperfusion. The activation of leukocytes and endothelial cells during reperfusion causes neutrophil adhesion in capillaries, resulting in plugging and further ischemia, Alternativety, neutrophil adhesion to endothelium leads to the migration of neutrophil with local edema formation, hemorrhage and thrombosis. Some chemotactic and activating factors are needed to propel neutrophils to the site of local inflammation. The chief cytikines that induce a pro-adhesive state in endothelium are tumor necrosis factor-alpha(TNF-alpha), interleukin-1 beta(IL-1 beta) and endotoxin or lipopolysaccharide(LPS). Similarly, TNF-alpha,and to a lesser extent interleukin-8(IL-8), is the important stimulus that acts on neutrophils and other leukocytes to alter their adhesion. The purpose of this study was to evaluate the pathogenetic role of IL-8 after perfusion with CDl8 monoclonal antibody(CDl8 mAb), the blocking antibody of neutrophil adherence, on reperfusion injury in rat epigastric island skin flap. A 6 X 3 cm-sized island skin flap was made on the abdomen. The epigastric pedicle was occluded for six hours with ambient temperature. Fifteen minutes before reperfusion, the flap was perfused with saline and CDl8 mAb(1 mg/kg). For evaluation of IL-8 levels, tissue fluid and serum were obtained at 4, 8, 12 and 24 hours after reperfusion. IL-8 concentrations of the CDl8 mAb group in the tissue fluid were significantly decreased at 8, 12 and 24 hours compared to the control group(P > 0.01), but the difference between the two groups was not significant at 4 hours after reperfusion IL-8 concentrations of the CDl8 mAb group in the serum were significantly decreased over time compared to the control group(P > 0.05, p > 0.01). Form the above results, we concluded that blocking neutrophil adherence using CD18 mAb within the peak level of IL-8 at 4 hours after reperfusion may be a better method of reducing reperfusion injury to the island skin flap.