Effects of β-IFN-1b treatment in MS patients on adhesion between PBMNCs, HUVECs and MS-HBECs: An in vivo and in vitro study

The in vivo effects on the expression of adhesion molecules and on the adhesion between mononuclear cells and multiple sclerosis human brain endothelial cells (MS-HBECs) were investigated at the beginning of β-IFN-1b treatment of MS patients. MS-HBECs were isolated from a surgical specimen obtained from an MS patient undergoing brain surgery for vascular aneurysm. 48 h after the first single administration of β-IFN-lb, PBMNCs of 10 MS patients were analyzed for HLA-DR, CD11a, CDI8 and VLA-4 expression and the adhesion between PBMNCs and both stimulated and unstimulated MS-HBECs evaluated. sICAM-1 and sVCAM-1 dosage in the serum of the patients was checked as well. The experiments were repeated using HUVECs in order to detect possible endothelial organ-specific differences. The experiments were also performed after six months of β-INF-lb treatment on HUVECs. No significant effects on mononuclear cells/endothelium adhesion were detected at 48 h, but adhesion of PBMNCs to HUVECs decreased at six months. An increase in HLA-DR and VLA-4 and a decrease of CD18 was detected in monocytes. The serum level of sVCAM-1 increased at T₂ and was still higher than at T₀ at six months. The effect of the β-IFN-1b treatment on both MS- HBECs and HUVECs, was selectively studied in vitro by testing the expression of cytokine-induced adhesion molecules HLA-DR, ICAM-1 and VCAM-1. The in vitro experiments confirmed that β-IFN-lb is able to antagonize γ-IFN- induced HLA-DR expression on MS human brain endothelial cells without relevant effects on VCAM-1 and ICAM-1.