ICAM-1 expression and fluid phase endocytosis (FPE) in cultured brain microvascular endothelial cells (BMECs) after exposure to recombinant Interferon β-la (IFβ-la) and TNFa

Treatment of relapsing-remitting (RR) multiple sclerosis (MS) with IFβ-la reduced relapse rate and gadolinium-enhanced MRI lesions (Jacobs et al, 1996). Cytokines like TNFa may contributr to blood brain barrier (BBB) breakdown which is associated with increased FPE and ICAM-1 expression by BMECs. We examined whether IFNβ-la affected ICAM-1 expression and FPE of horseradish peroxidase in cultured rat BMECs stimulated by TNF a. Treatment of BMECs monolayer with TNFa (100 U/ml) for 24 h significantly increased ICAM-1 expression and FPE, whereas 100-1000 U/ml EFNβ-la for 72 h did not modify baseline ICAM-1 and FPE levels. Incubation of BMEC with 1000 U/ml IFNβ-la for 48 h followed by combined IFβ -la and TNFa for 24 h significantly downregulated TNFa-induced elevation of ICAM 1 and FPE. The therapeutic effect of IFNβ-la on RR MS may involve direct regulatory actions on BMECs.