Inhibition of neutrophil-mediated acute inflammation injury by an antibody against interleukin-8 (IL-8)
Chemokines are a family of cytokines regulating the migration and functions of leukocytes in a cell-type specific manner. A prototype of C-X-C chemokines, interleukin-8 (IL-8), chemoattracts and activates neutrophils in vitro, and IL-8 concentrations in body fluids are markedly increased in several neutrophil-mediated acute inflammation. Moreover, we previously reported that the administration of a neutralizing antibody to IL-8 prevented neutrophil-mediated tissue injury, as well as neutrophil infiltration, in several animal disease models. These observations implicate IL-8 as a major mediator of neutrophil-mediated tissue injury. Furthermore, we recently showed that an anti-IL-8 antibody effectively prevented two models that are very relevant to clinical situations; endotoxemia-induced acute respiratory distress syndrome (ARDS)-like lung injury and cerebral reperfusion injury. These results raise the possibility that IL-8 is a novel target for therapeutic intervention in neutrophil-mediated acute inflammation.
Mukaida
N
N
Department of Molecular Pharmacology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan. naofumim@kenroku.kanazawa-u.ac.jp
Matsumoto
T
T
Yokoi
K
K
Harada
A
A
Matsushima
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002545:Brain Ischemia; D018925:Chemokines / Q000502:physiology; D019446:Endotoxemia; D005260:Female; D007116:Immunization, Passive; D007249:Inflammation / Q000517:prevention & control*; D016209:Interleukin-8 / Q000276:immunology* / Q000502:physiology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D018925:Chemokines; D016209:Interleukin-8; D017382:Reactive Oxygen Species