O. Stuve et al., INTERFERON BETA-1B DECREASES THE MIGRATION OF T-LYMPHOCYTES IN-VITRO - EFFECTS ON MATRIX METALLOPROTEINASE-9, Annals of neurology, 40(6), 1996, pp. 853-863
In multiple sclerosis (MS), the influx of activated T lymphocytes into
the brain parenchyma leads to the subsequent damage of oligodendrocyt
es, the cells that produce central nervous system (CNS) myelin. We rep
ort here that interferon beta-1b (IFN beta-1b), a drug shown to be eff
icacious in the treatment of patients with MS, decreases the in vitro
migration of activated T lymphocytes through fibronectin (FN), a major
component of the basement membrane that surrounds cerebral endotheliu
m. At 1,000 IU/ml, IFN beta-1b reduced the migratory rate to that of u
nactivated T cells. In contrast, IFN gamma at 1,000 IU/ml, which cause
d a similar decrease (25%) in the proliferation rate of T lymphocytes
as IFN beta-1b, did not affect migration. All T-lymphocyte subsets and
natural killer (NK) cells were demonstrated by Bow cytometry to be eq
ually affected by IFN beta-1b treatment. I-125-Western blot analyses r
evealed that IFN beta-1b treatment resulted in a marked reduction of t
he ability of T cells to cleave FN. The substrate-degrading capability
of T lymphocytes was shown to be due predominantly to the activity of
a 92-kd matrix metalloproteinase, MMP-3, whose levels were decreased
by IFN beta-1b. We suggest that the clinical benefits of IFN beta-1b t
reatment in MS patients may be in part a result of the ability of this
drug to significantly decrease MMP-9 activity, leading to a reduction
of T-lymphocyte infiltration into the CNS.