Interferon-Beta Prevents Cytokine-Induced Neutrophil Infiltration and Attenuates Blood–Brain Barrier Disruption

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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-β) 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-β 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 μg in 1 μL), 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-β (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-β treatment downregulated matrix metalloproteinase-9. IFN-β has already been approved for human use as a treatment for the chronic inflammatory disorder multiple sclerosis. The potential value of IFN-β as a treatment that can attenuate acute brain inflammation is considered.