Humanized monoclonal antibody against the chemokine CXCL-8 (IL-8) effectively prevents acute lung injury.
As one of the most important endogenous chemotactic factors for neutrophils, the chemokine CXCL8 (IL-8) is involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by massive neutrophil infiltration in the lung. Since neutralization of CXCL8 with polyclonal antibody has been shown to reduce the severity of ALI/ARDS in animal models, we explored the potential of humanized anti-CXCL8 antibody as a preventive or therapeutic agent for ALI. We used a 'two-hit' protocol to induce ALI in rabbits that showed extensive edema in the alveolar lumina, marked infiltration of neutrophils in the lung tissue, fibrin deposition in alveolar space, and destruction of pulmonary architecture, culminating in severe hypoxemia. Concomitant challenge with endotoxin after priming with oleic acid (OA) induced a marked elevation of CXCL8 level in bronchoalveolar lavage fluid. Treatment of the rabbits with a humanized anti-CXCL8 antibody prevented neutrophil infiltration in the lung in association with alleviated ALI syndrome. Our results indicate a promising future for utilization of humanized anti-CXCL8 antibody in the prevention and treatment of ALI and ARDS in human.
Bao
ZhiYao
Z
Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
Ye
QingWei
Q
Gong
WangHua
W
Xiang
Yi
Y
Wan
HuanYing
H
D055371:Acute Lung Injury / Q000517:prevention & control / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018893:Bronchoalveolar Lavage; D002199:Capillary Permeability / Q000276:immunology; D004487:Edema / Q000276:immunology; D004731:Endotoxins / Q000276:immunology; D005260:Female; D005337:Fibrin / Q000276:immunology; D000860:Hypoxia / Q000276:immunology; D007375:Interleukin-1 / Q000737:chemistry / Q000276:immunology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D019301:Oleic Acid / Q000276:immunology; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000517:prevention & control / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid; D005337:Fibrin