Production of IL-1β and IL-1Ra as risk factors for susceptibility and progression of relapse-onset multiple sclerosis

被引:101
作者
de Jong, BA
Huizinga, TWJ
Bollen, ELEM
Uitdehaag, BMJ
Bosma, GPT
van Buchem, MA
Remarque, EJ
Burgmans, ACS
Kalkers, NF
Polman, CH
Westendorp, RGJ
机构
[1] Leiden Univ, Ctr Med, Dept Internal Med, NL-2300 RC Leiden, Netherlands
[2] LUMC, Dept Clin Epidemiol, Leiden, Netherlands
[3] LUMC, Dept Rheumatol, Leiden, Netherlands
[4] LUMC, Dept Neurol, Leiden, Netherlands
[5] VU Med Ctr, Dept Neurol, Amsterdam, Netherlands
[6] LUMC, Dept Radiol, Leiden, Netherlands
[7] LUMC, Dept Gerontol, Leiden, Netherlands
[8] VU Med Ctr, MS MRI Ctr, Amsterdam, Netherlands
关键词
multiple sclerosis; immunogenetics; interleukin-1; polymorphisms; magnetization transfer ratio histogram analysis;
D O I
10.1016/S0165-5728(02)00056-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interleukin-1beta (IL-1beta) is present in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1Ra) moderates the induction of experimental autoimmune encephalomyelitis (EAE). Here, we show that families that are characterized by high over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p = 0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio. It is also related to the reduction of volumetric magnetization transfer ratio (MTR) histogram height, a measure of parenchymal integrity (p = 0.04). Those families who combine a high IL-1beta over IL-1Ra ratio with a high tumor necrosis factor (TNF) over IL-10 production ratio have a 6.2-fold (95% CI, 1.8-21; p = 0.002) increased risk. Innate production of IL-1beta and IL-1Ra is not related to the outcome of primary progressive MS. Taq1 polymorphism in the IL-1beta gene and the variable number of tandem repeats (VNTR) polymorphism of 86-base pairs within the IL-1Ra gene cannot explain these findings. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:172 / 179
页数:8
相关论文
共 52 条
[21]   Defining the clinical course of multiple sclerosis: Results of an international survey [J].
Lublin, FD ;
Reingold, SC .
NEUROLOGY, 1996, 46 (04) :907-911
[22]  
Lucchinetti C, 2000, ANN NEUROL, V47, P707, DOI 10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO
[23]  
2-Q
[24]   Distinct patterns of multiple sclerosis pathology indicates heterogeneity in pathogenesis [J].
Lucchinetti, CF ;
Bruck, W ;
Rodriguez, M ;
Lassmann, H .
BRAIN PATHOLOGY, 1996, 6 (03) :259-274
[25]   A study of interleukin-1 cluster genes in susceptibility to and severity of multiple sclerosis [J].
Luomala, M ;
Lehtimäki, T ;
Elovaara, I ;
Wang, XY ;
Ukkonen, M ;
Mattila, K ;
Laippala, P ;
Koivula, T ;
Hurme, M .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2001, 185 (02) :123-127
[26]  
Maniatis T., 1982, MOL CLONING A LAB MA
[27]   PROTECTIVE EFFECT OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL-1RA) ON EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN RATS [J].
MARTIN, D ;
NEAR, SL .
JOURNAL OF NEUROIMMUNOLOGY, 1995, 61 (02) :241-245
[28]   INCREASED INTERLEUKIN-1 PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN PATIENTS WITH MULTIPLE-SCLEROSIS [J].
MATSUDA, M ;
TSUKADA, N ;
MIYAGI, K ;
YANAGISAWA, N .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1991, 102 (01) :100-104
[29]   Circulating serum levels of IL-1ra in patients with relapsing remitting multiple sclerosis are normal during remission phases but significantly increased either during exacerbations or in response to IFN-beta treatment [J].
Nicoletti, F ;
Patti, F ;
DiMarco, R ;
Zaccone, P ;
Nicoletti, A ;
Meroni, PL ;
Reggio, A .
CYTOKINE, 1996, 8 (05) :395-400
[30]   Progress in determining the causes and treatment of multiple sclerosis [J].
Noseworthy, JH .
NATURE, 1999, 399 (6738) :A40-A47