title: P-selectin monoclonal antibody may attenuate the whole body inflammatory response induced by cardiopulmonary bypass.
abstract: Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been reported to be involved in the initiation of this inflammatory response by promoting the adhesion of neutrophils to endothelial cells in postcapillary venules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the effect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceutical) on the response of inflammatory cytokines and lung injury in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minutes (80 ml/kg per minute, 34 degrees C) under one of two conditions. In group P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circuit (n = 10). Saline alone was given to group C (n = 10). Inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1beta, IL-6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchange ability were measured 1) before the initiation of CPB, 2) at the termination of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1beta 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 increased in a pattern similar to that of the inflammatory cytokines and was significantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of inflammatory 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.
authors.affiliation: Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Sawa
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: S J
authors.initials: SJ
authors.lastname: Tojo
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Suhara
authors.forename: S
authors.initials: S
authors.lastname: Ohtake
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D007375:Interleukin-1 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000276:immunology*; D011014:Pneumonia / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha