Zx. Qu et al., ALL-TRANS-RETINOIC ACID POTENTIATES THE ABILITY OF INTERFERON BETA-1BTO AUGMENT SUPPRESSOR-CELL FUNCTION IN MULTIPLE-SCLEROSIS, Archives of neurology, 55(3), 1998, pp. 315-321
Objective: To determine the effects of combination all-trans retinoic
acid (RA) and interferon beta-1b therapy on immune system functions po
tentially relevant to multiple sclerosis (MS). Design: Interferon gamm
a-secreting cells, T suppressor cell function, and lymphocyte prolifer
ative responses were assayed using peripheral blood mononuclear cells
from patients with MS and control subjects under control conditions an
d in the presence of interferon beta-1b, RA, and the 2 combined. Setti
ng: A university hospital MS clinic. Participants: Seventeen patients
with secondarily progressive MS and 25 control subjects. Results: Inte
rferon beta-1b use increased interferon gamma-secreting cell counts, a
ugmented T suppressor cell function, and inhibited T-cell proliferatio
n. Therapy with RA decreased interferon gamma-secreting cell counts, h
ad a minimal positive effect on T suppressor cell function, and had no
effect on T-cell proliferation. When RA and interferon beta-1b were c
ombined, the inhibitory effect of RA on interferon gamma-secreting cel
ls predominated, T suppressor cell function increased synergistically
over the increment observed with interferon beta-1b use alone, and the
inhibitory effect of interferon beta-1b alone on T-cell proliferation
remained unchanged. Conclusions: Treatment with interferon beta-1b pa
rtially restores defective T suppressor cell function in patients with
MS. This potentially beneficial action is synergistically potentiated
by RA. Interferon beta-lb increases the number of interferon gamma-se
creting cells in the circulation when treatment is initiated. A simila
r increment in interferon gamma-secreting cells is observed when inter
feron beta-1b is added to cultural peripheral blood mononuclear cells
in vitro. This potentially deleterious action of interferon beta-1b is
reversed by RA. Interferon beta-1b inhibits lymphocyte proliferation
modestly but reproducibly. This action of interferon beta-1b is unalte
red by RA. These data provide a rationale for a trial of combination t
reatment with interferon beta-1b and RA in patients with MS.