Multiple sclerosis:: modulation of apoptosis susceptibility by glatiramer acetate

被引:10
作者
Aktas, O
Ari, N
Rieks, M
Hoffmann, V
Schimrigk, S
Przuntek, H
Pöhlau, D
机构
[1] Charite, Dept Neurol, Div Neuroimmunol, Berlin, Germany
[2] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-4630 Bochum, Germany
[3] Ruhr Univ Bochum, Dept Microbiol, D-4630 Bochum, Germany
[4] Kamillusklin, Dept Neurol, Asbach, Germany
来源
ACTA NEUROLOGICA SCANDINAVICA | 2001年 / 104卷 / 05期
关键词
multiple sclerosis; apoptosis; glatiramer acetate;
D O I
10.1034/j.1600-0404.2001.00125.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objectives - We investigated whether therapy of multiple sclerosis (MS) with glatiramer acetate (GA) involves the modulation of programmed cell death (apoptosis) in disease-relevant T-helper lymphocytes. Material and methods - Blood was drawn from 15 relapsing-remitting MS patients both before (baseline) as well as 6, 12, and 18 weeks after GA therapy and from 15 healthy controls. Detection of apoptosis was performed in response to in vitro stimulation with GA, myelin basic protein or medium alone. Results - T-helper lymphocytes from untreated MS patients displayed an overall increased apoptosis susceptibility in vitro, con pared to controls. During subsequent GA therapy, apoptosis vulnerability of these T cells in MS patients significantly declined under the initial baseline before treatment, and was finally equal in treated patients and controls. GA itself had no direct apoptosis-modulatory properties in vitro. Conclusion - Our findings indicate that therapy of multiple sclerosis with glatiramer acetate presumably involves the compensation of altered apoptosis in T-helper lymphocytes.
引用
收藏
页码:266 / 270
页数:5
相关论文
共 25 条
[1]  
BENNUN A, 1996, J NEUROL, V243, P14
[2]   PROTECTION FROM FAS-MEDIATED APOPTOSIS BY A SOLUBLE FORM OF THE FAS MOLECULE [J].
CHENG, JH ;
ZHOU, T ;
LIU, CD ;
SHAPIRO, JP ;
BRAUER, MJ ;
KIEFER, MC ;
BARR, PJ ;
MOUNTZ, JD .
SCIENCE, 1994, 263 (5154) :1759-1762
[3]   Soluble Fas (Apo-1) levels in cerebrospinal fluid of multiple sclerosis patients [J].
Ciusani, E ;
Frigerio, S ;
Gelati, M ;
Corsini, E ;
Dufour, A ;
Nespolo, A ;
La Mantia, L ;
Milanese, C ;
Massa, G ;
Salmaggi, A .
JOURNAL OF NEUROIMMUNOLOGY, 1998, 82 (01) :5-12
[4]   European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis [J].
Comi, G ;
Filippi, M ;
Wolinsky, JS .
ANNALS OF NEUROLOGY, 2001, 49 (03) :290-297
[5]   T-CELL DELETION IN HIGH ANTIGEN DOSE THERAPY OF AUTOIMMUNE ENCEPHALOMYELITIS [J].
CRITCHFIELD, JM ;
RACKE, MK ;
ZUNIGAPFLUCKER, JC ;
CANNELLA, B ;
RAINE, CS ;
GOVERMAN, J ;
LENARDO, MJ .
SCIENCE, 1994, 263 (5150) :1139-1143
[6]   T-cell apoptosis in autoimmune diseases: termination of inflammation in the nervous system and other sites with specialized immune-defense mechanisms [J].
Gold, R ;
Hartung, HP ;
Lassmann, H .
TRENDS IN NEUROSCIENCES, 1997, 20 (09) :399-404
[7]   Detection of the soluble form of the Fas molecule in patients with multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy [J].
Inoue, A ;
Koh, CS ;
Sakai, T ;
Yamazaki, M ;
Yanagisawa, N ;
Usuku, K ;
Osame, M .
JOURNAL OF NEUROIMMUNOLOGY, 1997, 75 (1-2) :141-146
[8]  
Ishigami T, 1998, EUR J IMMUNOL, V28, P1626, DOI 10.1002/(SICI)1521-4141(199805)28:05<1626::AID-IMMU1626>3.0.CO
[9]  
2-B
[10]   Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability [J].
Johnson, KP ;
Brooks, BR ;
Cohen, JA ;
Ford, CC ;
Goldstein, J ;
Lisak, RP ;
Myers, LW ;
Panitch, HS ;
Rose, JW ;
Schiffer, RB ;
Vollmer, T ;
Weiner, LP ;
Wolinsky, JS .
NEUROLOGY, 1998, 50 (03) :701-708