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

被引:98
作者
Veldhuis, TB
Floris, T
van der Meide, PH
Vos, IMP
de Vries, HE
Dijkstra, TD
Bär, PR
Nicolay, K
机构
[1] Univ Utrecht, Med Ctr, Image Sci Inst, Dept Expt Inv Vivo NMR, NL-3584 CJ Utrecht, Netherlands
[2] Univ Utrecht, Med Ctr, Lab Expt Neurol, Rudolf Magnus Inst Neurosci, NL-3584 CJ Utrecht, Netherlands
[3] VU Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands
[4] VU Med Ctr, Dept Pathol, Amsterdam, Netherlands
[5] Univ Utrecht, CLAI, Cytokine Biol Unit, Utrecht, Netherlands
关键词
interleukin-8; interferon-; beta; inflammation; neutrophil infiltration; blood-brain barrier; disruption; acute neurodegeneration;
D O I
10.1097/01.WCB.0000080701.47016.24
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mug in 1 muL), 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 10(6) 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 metalloprotemase-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.
引用
收藏
页码:1060 / 1069
页数:10
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