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

Research output: Contribution to journalArticleAcademicpeer-review

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-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
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 2003

Cite this

Veldhuis, Wouter B ; Floris, Sarah ; van der Meide, Peter H ; Vos, Ine M P ; de Vries, Helga E ; Dijkstra, Christien D ; Bär, Peter R ; Nicolay, Klaas. / Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption. In: Journal of Cerebral Blood Flow and Metabolism. 2003 ; Vol. 23, No. 9. pp. 1060-9.
@article{62a06313f3f6431b97dc7ce136f7b59a,
title = "Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption",
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-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.",
keywords = "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",
author = "Veldhuis, {Wouter B} and Sarah Floris and {van der Meide}, {Peter H} and Vos, {Ine M P} and {de Vries}, {Helga E} and Dijkstra, {Christien D} and B{\"a}r, {Peter R} and Klaas Nicolay",
year = "2003",
month = "9",
doi = "10.1097/01.WCB.0000080701.47016.24",
language = "English",
volume = "23",
pages = "1060--9",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "9",

}

Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption. / Veldhuis, Wouter B; Floris, Sarah; van der Meide, Peter H; Vos, Ine M P; de Vries, Helga E; Dijkstra, Christien D; Bär, Peter R; Nicolay, Klaas.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 23, No. 9, 09.2003, p. 1060-9.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption

AU - Veldhuis, Wouter B

AU - Floris, Sarah

AU - van der Meide, Peter H

AU - Vos, Ine M P

AU - de Vries, Helga E

AU - Dijkstra, Christien D

AU - Bär, Peter R

AU - Nicolay, Klaas

PY - 2003/9

Y1 - 2003/9

N2 - 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.

AB - 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.

KW - Animals

KW - Blood Volume

KW - Blood-Brain Barrier/drug effects

KW - Brain/anatomy & histology

KW - Cerebrovascular Circulation

KW - Endothelium, Vascular/cytology

KW - Hemodynamics

KW - Humans

KW - Intercellular Adhesion Molecule-1/metabolism

KW - Interferon-beta/immunology

KW - Interleukin-8/immunology

KW - Magnetic Resonance Imaging

KW - Male

KW - Matrix Metalloproteinase 9/metabolism

KW - Neurons/cytology

KW - Neutrophil Infiltration

KW - Neutrophils/immunology

KW - Rats

KW - Rats, Inbred F344

KW - Recombinant Proteins/pharmacology

U2 - 10.1097/01.WCB.0000080701.47016.24

DO - 10.1097/01.WCB.0000080701.47016.24

M3 - Article

VL - 23

SP - 1060

EP - 1069

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 9

ER -