Effects of rIFN-ss-1b on serum circulating ICAM-1 in relapsing remitting multiple sclerosis and on the membrane-bound ICAM-1 expression on brain microvascular endothelial cells

rIFN-beta reduces the frequency of the gadolinium-enhancing (Gd+) magnetic resonance imaging (MRI) lesions in relapsing remitting (RR) MS. Its mechani sm of action on improving the integrity of the blood-brain barrier (BBB) re mains unclear. We investigated the effect of rIFN-beta-1b on the soluble in tercellular adhesion molecule-1 (sICAM-1) serum levels (ELISA) in 36 RR MS patients receiving treatment with rIFN-beta for 1 year, and also the TNF-al pha-induced membrane-bound ICAM-1 (mICAM-1) expression on cultured rat brai n microvascular endothelial cells (BMECs). In vivo data showed that sICAM-1 serum levels at baseline significantly increased (P < 0.01) in 12 months o f rIFN-beta-1b treatment. The increase paralled a clinical and MRI improvem ent. In the second semester of the treatment the integrated area under the curve of Expanded Disability Status Score normalised to entry baseline (Del ta EDSS AUG) was significantly (P < 0.05) smaller than in the first semeste r. The percentage of patients with Gd+MRI decreased significantly (P < 0.05 ) in the first (33%) and second (29%) semesters of treatment compared to ba seline (62%). In vitro experiments showed that the incubation of BMEC monol ayer with 100 u/ml of TNF-alpha for 24 h significantly (P < 0.05) increased mICAM-1 expression, whereas 2000 u/ml of rIFN-beta-1b for 72 h did not mod ify the baseline levels. The incubation of BMEC with 2000 u/ml of rLFN-beta -1b for 48 h followed by combined IFN-beta-lb and TNF-a for 24 h significan tly (P < 0.05) downregulated TNF-alpha-induced mICAM-1 expression. These re sults suggest that the effect of rIFN-beta-1b on the BBB may be mediated by changes in both sICAM-1 serum levels and mICAM-1 BMEC expression.