Interferon-beta prevents interleukin-8-induced neutrophil infiltration and attenuates blood-brain barrier disruption

W.B. Veldhuis, S. Floris, P.H. Meide, van der, I.P.M. Vos, H.E. Vries, de, C.D. Dijkstra, P.R. Baer, K. Nicolaij

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    Abstract

    Inflammation can contribute to brain injury, such as that resulting from ischemia or trauma. The authors have previously shown that the cytokine interferon-beta (IFN-) affords protection against ischemic brain injury, which was associated with a diminished infiltration of neutrophils and a reduction in blood–brain barrier (BBB) disruption. The goal of the current study was to directly assess the effects of IFN- on neutrophil infiltration, with the use of an in vivo assay of neutrophil infiltration with relevance to ischemic brain injury. Intrastriatal injection of recombinant rat cytokine–induced neutrophil chemoattractant-1, a member of the interleukin-8 family (1 g in 1 L), triggered massive infiltration of neutrophils and extensive BBB disruption 6 hours later, as measured using immunofluorescence microscopy and magnetic resonance imaging in the rat, respectively. Depleting the animals of neutrophils before interleukin-8 injection prevented BBB disruption. Treatment with IFN- (5 106 U/kg) almost completely prevented neutrophil infiltration and attenuated BBB damage. Gelatinase zymography showed matrix metalloproteinase-9 expression in the ipsilateral striatum after interleukin-8 injection. Both neutrophil depletion and IFN- treatment downregulated matrix metalloproteinase-9. IFN- has already been approved for human use as a treatment for the chronic inflammatory disorder multiple sclerosis. The potential value of IFN- as a treatment that can attenuate acute brain inflammation is considered.
    Original languageEnglish
    Pages (from-to)1060-1069
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume23
    Issue number9
    DOIs
    Publication statusPublished - 2003

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