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

Wouter B Veldhuis, Sarah Floris, Peter H van der Meide, Ine M P Vos, Helga E de Vries, Christien D Dijkstra, Peter R Bär, Klaas Nicolay

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106 Citations (Scopus)


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-beta) 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-beta 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 microg in 1 microl), 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-beta (5 x 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-beta treatment downregulated matrix metalloproteinase-9. IFN-beta has already been approved for human use as a treatment for the chronic inflammatory disorder multiple sclerosis. The potential value of IFN-beta as a treatment that can attenuate acute brain inflammation is considered.

Original languageEnglish
Pages (from-to)1060-9
Number of pages10
JournalJournal of cerebral blood flow and metabolism
Issue number9
Publication statusPublished - Sept 2003


  • Animals
  • Blood Volume
  • Blood-Brain Barrier/drug effects
  • Brain/anatomy & histology
  • Cerebrovascular Circulation
  • Endothelium, Vascular/cytology
  • Hemodynamics
  • Humans
  • Intercellular Adhesion Molecule-1/metabolism
  • Interferon-beta/immunology
  • Interleukin-8/immunology
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 9/metabolism
  • Neurons/cytology
  • Neutrophil Infiltration
  • Neutrophils/immunology
  • Rats
  • Rats, Inbred F344
  • Recombinant Proteins/pharmacology

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