Decreased integrin gene expression in patients with MS responding to interferon-beta treatment.
Interferon-beta (IFN-beta) ameliorates disease course in a subset of patients with MS. The reasons for heterogeneity of clinical responses, however, are unclear. We assessed possible effects of IFN-beta on the gene expression of the leukocyte adhesion molecules VLA-4 and LFA-1 during the first year of treatment of 50 patients with relapsing-remitting MS who showed differential clinical responses. We observed a significant reduction of VLA-4 (P=0.002) and LFA-1 (P=0.03) mRNA expression compared to baseline in first-year clinical responders (n=22). In contrast, first-year IFN-beta non-responders (n=28) had unchanged levels of VLA-4 and LFA-1. In vitro treatment of PBMC with IFN-beta indicated a direct effect on transcription of the integrins' genes. Transcriptional downmodulation of adhesion molecules during IFN-beta treatment may contribute to its mode of action in MS.
Muraro
P A
PA
Neuroimmunology Unit, Department of Oncology and Neuroscience, Medical School, University G. D'Annunzio, Via dei Vestini, Chieti 66013, Italy. murarop@ninds.nih.gov
Liberati
L
L
Bonanni
L
L
Pantalone
A
A
Caporale
C M
CM
Iarlori
C
C
De Luca
G
G
Farina
D
D
Lugaresi
A
A
Gambi
D
D
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D016899:Interferon-beta; D000068556:Interferon beta-1a