P-selectin monoclonal antibody may attenuate the whole body inflammatory response induced by cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been repo rted to be involved in the initiation of this inflammatory response by prom oting the adhesion of neutrophils to endothelial cells in postcapillary ven ules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the ef fect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumito mo Pharmaceutical) on the response of inflammatory cytokines and lung injur y in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minut es (80 ml/kg per minute, 34 degrees C) under one of two conditions. In grou p P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circu it (n = 10). Saline alone was given to group C (0 = 10). Inflammatory cytok ines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1 beta , IL- 6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchan ge ability were measured 1) before the initiation of CPB, 2) at the termina tion of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1 beta was detected during the experimental period in either group. The plasma levels of IL-6 and IL-8 increased after CPB in both groups, but they were significantly lower in group P than in group C. The RI value inc reased in a pattern similar to that of the inflammatory cytokines and was s ignificantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of i nflammatory cytokines and attenuates CPB induced lung injury in rats. Thus, P-selectin may play a role in the augmentation of CPB induced inflammatory response, and the use of its inhibitory monoclonal antibody seems to be a promising strategy for the treatment of CPB induced lung injury.