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From the Departments of Neurological and Psychiatric Sciences (Drs. Trojano, Avolio, Ruggieri, Defazio, Liguori, Paolicelli, Giuliani, and Livrea) and Biochemistry and Molecular Biology (Drs. Liuzzi and Santacroce), University of Bari; and the Department of Biology D.B.A.F. (Dr. Riccio), University of Basilicata, Potenza, Italy.
Address correspondence and reprint requests to Dr. Maria Trojano, Department of Neurological and Psychiatric Sciences, University of Bari, Policlinico, Piazza G. Cesare, 70124 Bari, Italy; e-mail: livrea{at}cimedoc.uniba.it
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 (rIFNß)-1b.
BACKGROUND: rIFNß 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 (
EDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNß-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, 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 sixth, 12th, and 18th months; and a greater EDSS AUC in the third semester of treatment in comparison with the NAB- patients.
CONCLUSIONS: These results show that rIFNß-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.
Key words: MS—rIFNß-1b—Soluble ICAM-1—Matrix metalloproteinases.
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