ICAM 1 expression and fluid phase endocytosis of cultured brain microvascular endothelial cells following exposure to interferon β-1a and TNFα

We have studied the effect of interferon (IF) beta-1a on the basal and TNF alpha-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 IF beta-1a. ICAM 1 induction and FPE enhancement caused by 100 U/ml TNF alpha for 24 h was not influenced by simultaneous administration of 1000 U/ml IF beta-1a. Treatment of cultures with IF beta-1a for 48 h followed by 24-h coincubation with TNF alpha (100 U/ml) and IF beta-1a (1000 U/ml) resulted in significant downregulation of TNF alpha-induced ICAM 1 expression and FPE. Downregulation of TNF alpha-induced ICAM 1 expression was not observed when combined treatment with TNF alpha (100 U/ml) and IF beta-1a (1000 U/ml) for 24 h was followed by 48 h exposure to IF beta-1a. We concluded that the blood-brain barrier endothelium may be a target of IF beta-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 IF beta-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. (C) 1998 Elsevier Science B.V. All rights reserved.