Changes of serum sICAM-1 and MMP-9 induced by rIFNβ-1b treatment in relapsing-remitting MS

被引:112
作者
Trojano, M
Avolio, C
Liuzzi, GM
Ruggieri, M
Defazio, G
Liguori, M
Santacroce, MP
Paolicelli, D
Giuliani, F
Riccio, P
Livrea, P
机构
[1] Univ Bari Policlin, Dept Neurol & Psychiat Sci, I-70124 Bari, Italy
[2] Univ Bari, Dept Biochem & Mol Biol, I-70124 Bari, Italy
[3] Univ Basilicata, Dept Biol, I-85100 Potenza, Italy
关键词
MS; rIFN beta-1b; soluble ICAM-1; matrix metalloproteinases;
D O I
10.1212/WNL.53.7.1402
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To correlate changes in serum levels of intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases(MMP) with clinical and MRI evidence of disease activity in MS patients receiving treatment with interferon-beta (rIFN beta)-1b. Background: rIFN beta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechanism of action on improving the integrity of the blood-brain barrier remains unclear. Methods: sICAM-1 and MMP-9 and MMP-2 serum levels were longitudinally (24 months) investigated (ELISA; zymography) in correlation with the modifications of the integrated area under the curve of Expanded Disability Status Scale scores normalized to entry baseline (Delta EDSS AUG) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFN beta-1b production (MxA) in 36 RRMS patients. Results: During the first 12 months of treatment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 were significantly negatively correlated. MMP-2 levels did not change significantly during the same period. During the second semester of the study, Delta EDSS AUC was significantly reduced. The percentage of patients with Gd+ MRI decreased significantly in the first (33%), second (29%), third (20%), and fourth (28%) semesters of treatment compared to baseline (62%). The NAB+ patients (14%) tended to have lower sICAM-1 levels at the ninth month; a higher MMP-9 activity at the girth, 12th, and 18th months; and a greater Delta EDSS AUC in the third semester of treatment in comparison with the NAB- patients. Conclusions: These results show that rIFN beta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.
引用
收藏
页码:1402 / 1408
页数:7
相关论文
共 47 条
[1]   INHIBITION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY AN ANTIBODY TO THE INTERCELLULAR-ADHESION MOLECULE ICAM-1 [J].
ARCHELOS, JJ ;
JUNG, S ;
MAURER, M ;
SCHMIED, M ;
LASSMANN, H ;
TAMATANI, T ;
MIYASAKA, M ;
TOYKA, KV ;
HARTUNG, HP .
ANNALS OF NEUROLOGY, 1993, 34 (02) :145-154
[2]   VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta [J].
Calabresi, PA ;
Pelfrey, CM ;
Tranquill, LR ;
Maloni, H ;
McFarland, HF .
NEUROLOGY, 1997, 49 (04) :1111-1116
[3]   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
[4]  
CANNELLA B, 1991, LAB INVEST, V65, P23
[5]   Matrix metalloproteinases degrade myelin basic protein [J].
Chandler, S ;
Coates, R ;
Gearing, A ;
Lury, J ;
Wells, G ;
Bone, E .
NEUROSCIENCE LETTERS, 1995, 201 (03) :223-226
[6]   Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor [J].
Clements, JM ;
Cossins, JA ;
Wells, GMA ;
Corkill, DJ ;
Helfrich, K ;
Wood, LM ;
Pigott, R ;
Stabler, G ;
Ward, GA ;
Gearing, AJH ;
Miller, KM .
JOURNAL OF NEUROIMMUNOLOGY, 1997, 74 (1-2) :85-94
[7]   EDMUS, A EUROPEAN DATABASE FOR MULTIPLE-SCLEROSIS [J].
CONFAVREUX, C ;
COMPSTON, DAS ;
HOMMES, OR ;
MCDONALD, WI ;
THOMPSON, AJ .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1992, 55 (08) :671-676
[8]   The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: Comparison of stages in lesion evolution [J].
Cuzner, ML ;
Gveric, D ;
Strand, C ;
Loughlin, AJ ;
Paemen, L ;
Opdenakker, G ;
Newcombe, J .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1996, 55 (12) :1194-1204
[9]   Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system [J].
Cuzner, ML ;
Opdenakker, G .
JOURNAL OF NEUROIMMUNOLOGY, 1999, 94 (1-2) :1-14
[10]   ICAM 1 expression and fluid phase endocytosis of cultured brain microvascular endothelial cells following exposure to interferon β-1a and TNFα [J].
Defazio, G ;
Trojano, M ;
Ribatti, D ;
Nico, B ;
Giorelli, M ;
De Salvia, R ;
Russo, G ;
Roncali, L ;
Livrea, P .
JOURNAL OF NEUROIMMUNOLOGY, 1998, 88 (1-2) :13-20