Effects of beta-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 beta-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 beta-IFN-1b, PBMNCs of 10 MS patients were analyzed for HLA-DR, CD11a, CD18 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 beta-INF-1b 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 beta-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 beta-IFN-1b is able to antagonize gamma-IFN-induced HLA-DR expression on MS human brain endothelial cells without relevant effects on VCAM-1 and ICAM-1.
Corsini
E
E
Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Gelati
M
M
Dufour
A
A
Massa
G
G
Nespolo
A
A
Ciusani
E
E
Milanese
C
C
La Mantia
L
L
Salmaggi
A
A
D000328:Adult; D000941:Antigens / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014471:Umbilical Veins / Q000473:pathology / Q000503:physiopathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000941:Antigens; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a