Effects of rIFN-beta-1b on serum circulating ICAM-1 in relapsing remitting multiple sclerosis and on the membrane-bound ICAM-1 expression on brain microvascular endothelial cells.
rIFN-beta reduces the frequency of the gadolinium-enhancing (Gd+) magnetic resonance imaging (MRI) lesions in relapsing remitting (RR) MS. Its mechanism of action on improving the integrity of the blood-brain barrier (BBB) remains unclear. We investigated the effect of rIFN-beta-1b on the soluble intercellular adhesion molecule-1 (sICAM-1) serum levels (ELISA) in 36 RR MS patients receiving treatment with rIFN-beta for 1 year, and also the TNF-alpha - induced membrane-bound ICAM-1 (mICAM-1) expression on cultured rat brain microvascular endothelial cells (BMECs). In vivo data showed that sICAM-1 serum levels at baseline significantly increased (P<0.01) in 12 months of rIFN-beta-1b treatment. The increase paralleled a clinical and MRI improvement. In the second semester of the treatment the integrated area under the curve of Expanded Disability Status Score normalised to entry baseline (DeltaEDSS AUC) was significantly (P<0.05) smaller than in the first semester. The percentage of patients with Gd+MRI decreased significantly (P<0.05) in the first (33%) and second (29%) semesters of treatment compared to baseline (62%). In vitro experiments showed that the incubation of BMEC monolayer with 100 u/ml of TNF-alpha for 24 h significantly (P<0.05) increased mICAM-1 expression, whereas 2000 u/ml of rIFN-beta-1b for 72 h did not modify the baseline levels. The incubation of BMEC with 2000 u/ml of rIFN-beta-1b for 48 h followed by combined IFN-beta-1b and TNF-alpha for 24 h significantly (P<0.05) downregulated TNF-alpha-induced mICAM-1 expression. These results suggest that the effect of rIFN-beta-1b on the BBB may be mediated by changes in both sICAM-1 serum levels and mICAM-1 BMEC expression.
Trojano
M
M
Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy.
Defazio
G
G
Avolio
C
C
Paolicelli
D
D
Giuliani
F
F
Giorelli
M
M
Livrea
P
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005682:Gadolinium; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation / Q000276:immunology; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D051381:Rats; D012995:Solubility
D000276:Adjuvants, Immunologic; D018799:Intercellular Adhesion Molecule-1; D000068576:Interferon beta-1b; D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a