Effective combination of minocycline and interferon-β in a model of multiple sclerosis

被引:58
作者
Giuliani, F
Fu, SA
Metz, LM
Yong, VW
机构
[1] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada
[2] Univ Calgary, Dept Oncol, Calgary, AB, Canada
[3] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada
基金
加拿大健康研究院;
关键词
EAE; multiple sclerosis; neuroprotection;
D O I
10.1016/j.jneuroim.2005.04.020
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The objective of the current study was to investigate whether minocycline improves the effect of an existing multiple sclerosis (MS) medication, interferon-beta, on experimental autoimmune encephalomyelitis (EAE) in mice. When used at sub-optimal doses, neither medication affected EAE but their combination at these doses led to the significant alleviation of EAE disease severity scores and histological outcomes. In culture, the toxicity of T cells to neurons was alleviated by their prior exposure to minocycline or interferon-beta and their combination further attenuated neuronal death. Collectively, these results suggest the utility of the combination of minocycline and interferon-beta in MS. (C) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:83 / 91
页数:9
相关论文
共 64 条
[1]   Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury [J].
Arvin, KL ;
Han, BH ;
Du, YS ;
Lin, SZ ;
Paul, SM ;
Holtzman, DM .
ANNALS OF NEUROLOGY, 2002, 52 (01) :54-61
[2]   Human monocyte-derived dendritic cells produce bioactive gelatinase B:: Inhibition by IFN-ß [J].
Bartholomé, EJ ;
Van Aelst, I ;
Koyen, E ;
Kiss, R ;
Willems, F ;
Goldman, M ;
Opdenakker, G .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2001, 21 (07) :495-501
[3]   Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences [J].
Bjartmar, C ;
Trapp, BD .
CURRENT OPINION IN NEUROLOGY, 2001, 14 (03) :271-278
[4]  
Brod SA, 2000, ANN NEUROL, V47, P127, DOI 10.1002/1531-8249(200001)47:1<127::AID-ANA22>3.0.CO
[5]  
2-1
[6]   Targeting leukocyte MMPs and transmigration - Minocycline as a potential therapy for multiple sclerosis [J].
Brundula, V ;
Rewcastle, NB ;
Metz, LM ;
Bernard, CC ;
Yong, VW .
BRAIN, 2002, 125 :1297-1308
[7]   Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b [J].
Calabresi, PA ;
Tranquill, LR ;
Dambrosia, JM ;
Stone, LA ;
Maloni, H ;
Bash, CN ;
Frank, JA ;
McFarland, HF .
ANNALS OF NEUROLOGY, 1997, 41 (05) :669-674
[8]   An open-label trial of combination therapy with interferon β-1a and oral methotrexate in MS [J].
Calabresi, PA ;
Wilterdink, JL ;
Rogg, JM ;
Mills, P ;
Webb, A ;
Whartenby, KA .
NEUROLOGY, 2002, 58 (02) :314-317
[9]   MINOCYCLINE EXCRETION AND DISTRIBUTION IN RELATION TO RENAL-FUNCTION IN MAN [J].
CARNEY, S ;
BUTCHER, RA ;
DAWBORN, JK ;
PATTISON, G .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1974, 1 (04) :299-308
[10]   Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease [J].
Chen, M ;
Ona, VO ;
Li, MW ;
Ferrante, RJ ;
Fink, KB ;
Zhu, S ;
Bian, J ;
Guo, L ;
Farrell, LA ;
Hersch, SM ;
Hobbs, W ;
Vonsattel, JP ;
Cha, JHJ ;
Friedlander, RM .
NATURE MEDICINE, 2000, 6 (07) :797-+