Interferon-β treatment in multiple sclerosis patients decreases the number of circulating T cells producing interferon-γ and interleukin-4

被引:63
作者
Furlan, R
Bergami, A
Lang, R
Brambilla, E
Franciotta, D
Martinelli, V
Comi, G
Panina, P
Martino, G
机构
[1] Ist Sci San Raffaele, Dept Neurosci, DIBIT, Neuroimmunol Unit, I-20132 Milan, Italy
[2] Roche Milano Ric, I-20132 Milan, Italy
[3] Univ Pavia, Fdn Mondino, Lab Neuroimmunol, I-27100 Pavia, Italy
[4] Ist Sci San Raffaele, Dept Neurol, Multiple Sclerosis Ctr, I-20132 Milan, Italy
关键词
multiple sclerosis; interferon-beta; T helper cells; intracellular cytokine staining;
D O I
10.1016/S0165-5728(00)00377-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Systemic administration of interferon (IFN)-beta has been recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The immunological mechanism by which IFN-beta ameliorates MS is still partially unknown. We measured the number of blood circulating CD4(-), CD4(-), CD8(+), and CD8(-) T cells secreting IFN-gamma acid IL-4 in 26 RRMS patients followed or up to 9 months of an alternate day s.c. treatment with 8x6 IU of IFN-beta 1b. Compared to pre-treatment values, a significant (P<0.05) reduction of CD4(+). CD4(-), CD8(+) and CD8(-) cells producing IFN-<gamma> and of CD4(+) and CD4(-) cells producing IL-4 was observed in MS patients. The IFN-beta -associated effect was evident soon after the beginning of the treatment and persisted for the entire follow-up period. We did not observe any effect of IFN-beta treatment on the percentage of IL-4-producing CD8(+) and CD8(-) cells nor in that of natural killer (NK) cells producing IFN-gamma. Our results show that IFN-beta treatment in MS patients induces a profound and persistent down-regulation of the number of circulating T cells secreting IFN-gamma and IL-4 thus suggesting a broader rather than a specific immunomodulatory effect of IFN-beta in MS. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:86 / 92
页数:7
相关论文
共 35 条
[1]   Functional diversity of helper T lymphocytes [J].
Abbas, AK ;
Murphy, KM ;
Sher, A .
NATURE, 1996, 383 (6603) :787-793
[2]  
Becher B, 1999, ANN NEUROL, V45, P247, DOI 10.1002/1531-8249(199902)45:2<247::AID-ANA16>3.0.CO
[3]  
2-U
[4]   INCREASED PRODUCTION OF INTERFERON GAMMA AND TUMOR NECROSIS FACTOR PRECEDES CLINICAL MANIFESTATION IN MULTIPLE-SCLEROSIS - DO CYTOKINES TRIGGER OFF EXACERBATIONS [J].
BECK, J ;
RONDOT, P ;
CATINOT, L ;
FALCOFF, E ;
KIRCHNER, H ;
WIETZERBIN, J .
ACTA NEUROLOGICA SCANDINAVICA, 1988, 78 (04) :318-323
[5]   Mouse CD1-specific NK1 T cells: Development, specificity, and function [J].
Bendelac, A ;
Rivera, MN ;
Park, SH ;
Roark, JH .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :535-562
[6]   Cytokine gene expression in cells derived from CSF of multiple sclerosis patients [J].
Calabresi, PA ;
Tranquill, LR ;
McFarland, HF ;
Cowan, EP .
JOURNAL OF NEUROIMMUNOLOGY, 1998, 89 (1-2) :198-205
[7]   Interferon-gamma-secreting cells in multiple sclerosis patients treated with interferon beta-1b [J].
Dayal, AS ;
Jensen, MA ;
Lledo, A ;
Arnason, BGW .
NEUROLOGY, 1995, 45 (12) :2173-2177
[8]   INTERFERON BETA-1B IS EFFECTIVE IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS - CLINICAL-RESULTS OF A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL [J].
DUQUETTE, P ;
GIRARD, M ;
DESPAULT, L ;
DUBOIS, R ;
KNOBLER, RL ;
LUBLIN, FD ;
KELLEY, L ;
FRANCIS, GS ;
LAPIERRE, Y ;
ANTEL, J ;
FREEDMAN, M ;
HUM, S ;
GREENSTEIN, JI ;
MISHRA, B ;
MULDOON, J ;
WHITAKER, JN ;
EVANS, BK ;
LAYTON, B ;
SIBLEY, WA ;
LAGUNA, J ;
KRIKAWA, J ;
PATY, DW ;
OGER, JJ ;
KASTRUKOFF, LF ;
MOORE, GRW ;
HASHIMOTO, SA ;
MORRISON, W ;
NELSON, J ;
GOODIN, DS ;
MASSA, SM ;
GUTTERIDGE, E ;
ARNASON, BGW ;
NORONHA, A ;
REDER, AT ;
MARTIA, R ;
EBERS, GC ;
RICE, GPA ;
LESAUX, J ;
JOHNSON, KP ;
PANITCH, HS ;
BEVER, CT ;
CONWAY, K ;
WALLENBERG, JC ;
BEDELL, L ;
VANDENNOORT, S ;
WEINSHENKER, B ;
WEISS, W ;
REINGOLD, S ;
PACHNER, A ;
TAYLOR, W .
NEUROLOGY, 1993, 43 (04) :655-661
[9]   Interferon beta-1b treatment modulates TNFα and IFNγ spontaneous gene expression in MS [J].
Gayo, A ;
Mozo, L ;
Suarez, A ;
Tuñón, A ;
Lahoz, C ;
Gutiérrez, C .
NEUROLOGY, 1999, 52 (09) :1764-1770
[10]   Immunological effects of in vivo interferon-β1b treatment in ten patients with multiple sclerosis:: a 1-year follow-up [J].
Gelati, M ;
Corsini, E ;
Dufour, A ;
Massa, G ;
La Mantia, L ;
Milanese, C ;
Nespolo, A ;
Salmaggi, A .
JOURNAL OF NEUROLOGY, 1999, 246 (07) :569-573