ICAM 1 expression and fluid phase endocytosis of cultured brain microvascular endothelial cells following exposure to interferon beta-1a and TNFalpha.

We have studied the effect of interferon (IF) beta-1a on the basal and TNFalpha-induced intercellular adhesion molecule 1 (ICAM 1) expression and fluid phase endocytosis (FPE) of horseradish peroxidase in cultured rat brain microvascular endothelial cells. Neither basal ICAM 1 expression nor basal FPE were significantly affected by 24-72 h exposure to 1000 U/ml IFbeta-1a. ICAM 1 induction and FPE enhancement caused by 100 U/ml TNFalpha for 24 h was not influenced by simultaneous administration of 1000 U/ml IFbeta-1a. Treatment of cultures with IFbeta-1a for 48 h followed by 24-h coincubation with TNFalpha (100 U/ml) and IFbeta-1a (1000 U/ml) resulted in significant downregulation of TNFalpha-induced ICAM 1 expression and FPE. Downregulation of TNFalpha-induced ICAM 1 expression was not observed when combined treatment with TNFalpha (100 U/ml) and IFbeta-1a (1000 U/ml) for 24 h was followed by 48 h exposure to IFbeta-1a. We concluded that the blood-brain barrier endothelium may be a target of IFbeta-1a. Further, these in vitro findings may correlate with the results of recent clinical trials indicating that chronic treatment of relapsing remitting multiple sclerosis with IFbeta-1a prevents both clinical exacerbations and the appearance on Magnetic Resonance Imaging of new lesions enhanced by gadolinium which is taken up by increased transendothelial fluid phase vesicular transport.