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

Objective: To correlate changes in serum levels of intercellular adhesion m olecule-1 (sICAM-1) and matrix metalloproteinases(MMP) with clinical and MR I evidence of disease activity in MS patients receiving treatment with inte rferon-beta (rIFN beta)-1b. Background: rIFN beta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechan ism 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 longitudin ally (24 months) investigated (ELISA; zymography) in correlation with the m odifications 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 product ion (MxA) in 36 RRMS patients. Results: During the first 12 months of treat ment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 wer e significantly negatively correlated. MMP-2 levels did not change signific antly during the same period. During the second semester of the study, Delt a EDSS AUC was significantly reduced. The percentage of patients with Gd+ M RI decreased significantly in the first (33%), second (29%), third (20%), a nd 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 h igher MMP-9 activity at the girth, 12th, and 18th months; and a greater Del ta EDSS AUC in the third semester of treatment in comparison with the NAB- patients. Conclusions: These results show that rIFN beta-1b therapy increas es sICAM-1 serum levels and reduces serum MMP-9 activity.