Migratory behavior of lymphocytes isolated from multiple sclerosis patients: effects of interferon beta-1b therapy.
Previous reports by our group and by others have shown that in vitro treatment of T cells derived from healthy, normal subjects with interferon beta-1b (IFN-beta1b) reduces metalloproteinase (metalloproteinase type 9 [MMP-9]) activity with a consequent reduction in lymphocyte migration. In this study, we used a Boyden chamber assay to assess the migratory capacity of T cells derived from multiple sclerosis patients who either did or did not receive IFN-beta1b. Lymphocytes derived from patients treated for less than 2 years with IFN-beta migrated at a low rate that was indistinguishable from that of cells isolated from healthy donors. However, longer term treatment with IFN (>3.5 years) was associated with a reversion of the migration to a high level that did not differ statistically from that of cells isolated from untreated multiple sclerosis patients. For both high-migratory groups, migration could be reduced to control levels after the exogenous addition of TIMP-1, a relatively specific inhibitor of the MMP-9, implicating this protease in the process of T-cell migration. Our findings suggest that one of the mechanisms by which IFN-beta exerts its action is by reducing MMP-9 activity and thus the entry of inflammatory cells into the nervous system and, as such, MMPs may constitute potential therapeutic targets in inflammatory diseases such as multiple sclerosis.
Uhm
J H
JH
Department of Neuroimmunology, Montreal Neurological Hospital and Institute, McGill University, Quebec, Canada.
Dooley
N P
NP
Stuve
O
O
Francis
G S
GS
Duquette
P
P
Antel
J P
JP
Yong
V W
VW
D000328:Adult; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000503:physiopathology / Q000628:therapy*; D012008:Recurrence; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*
D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a