J Cereb Blood Flow Metab. 2003 Sep;23(9):1060-1069
Veldhuis WB, Floris S, Van Der Meide PH, Vos IM, De Vries HE, Dijkstra CD, Bar PR, Nicolay K.
Department of Experimental in vivo NMR, Image Sciences Institute and dagger Laboratory for Experimental Neurology, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, The Netherlands; double dagger Department of Molecular Cell Biology and paragraph sign Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; section sign Cytokine Biology Unit, CLAI, Utrecht University, Utrecht, The Netherlands.
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.