title: Prevention of cerebral edema and infarct in cerebral reperfusion injury by an antibody to interleukin-8.
abstract: Reperfusion after a transient ischemia is a frequently encountered clinical condition that often causes greater tissue damage than persistent ischemia itself. Reperfusion to rabbit brain, after a transient focal ischemia, induced neutrophil infiltration and aggregation--neither of which were observed in rabbit brain rendered ischemic alone for the same time interval--thereby leading to severe brain edema and infarct. Brain tissue levels of interleukin-8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), increased significantly at 6 hours after reperfusion, but without a noticeable elevation of plasma IL-8 levels. Moreover, we detected IL-8 protein immunohistologically in the vascular wall and, to a lesser degree, in infiltrated neutrophils, suggesting a local production of IL-8 in reperfused brain tissues. Furthermore, a neutralizing anti-IL-8 antibody significantly reduced brain edema and infarct size in comparison to rabbits receiving a control antibody. These results implicate locally produced IL-8 as a pivotal mediator of cerebral reperfusion and suggest that IL-8 is a novel target for the intervention of this injury.
authors.affiliation: Department of Neurosurgery, School of Medicine, Kanazawa University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: A
authors.initials: A
authors.lastname: Harada
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: J
authors.initials: J
authors.lastname: Yamashita
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000517:prevention & control*; D005260:Female; D016209:Interleukin-8 / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D016209:Interleukin-8