Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS.
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 (rIFNbeta)-1b.


BACKGROUND
rIFNbeta 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 (deltaEDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNbeta-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, deltaEDSS 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 sixth, 12th, and 18th months; and a greater deltaEDSS AUC in the third semester of treatment in comparison with the NAB- patients.


CONCLUSIONS
These results show that rIFNbeta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.
Trojano
M
M
Department of Neurological and Psychiatric Sciences, University of Bari, Italy. livrea@cimedoc.uniba.it
Avolio
C
C
Liuzzi
G M
GM
Ruggieri
M
M
Defazio
G
G
Liguori
M
M
Santacroce
M P
MP
Paolicelli
D
D
Giuliani
F
F
Riccio
P
P
Livrea
P
P
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000032:analysis; D004185:Disability Evaluation; D005260:Female; D005682:Gadolinium; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012008:Recurrence; D012995:Solubility
D000276:Adjuvants, Immunologic; D000906:Antibodies; D018799:Intercellular Adhesion Molecule-1; D000068576:Interferon beta-1b; D016899:Interferon-beta; D005682:Gadolinium; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000068556:Interferon beta-1a