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All-trans Retinoic Acid Plus
Interferon-ß-1B
In Multiple Sclerosis



Qu ZX; Dayal A; Jensen MA; Arnason BG
Arch Neurol 55: 315-21 (1998)
Univ of Chicago, Dept of Neurology and the Brain Research Institute, Chicago, Ill 60637, USA
U I #98178827
Abstract

Objective
To determine the effects of combination all-trans Retinoic Acid (RA) and Interferon-ß-1b therapy on Immune System Functions, potentially relevant to Multiple Sclerosis (MS).

Design
Interferon gamma-secreting cells, T-Suppressor cell function, and Lymphocyte proliferative responses were assayed using peripheral blood MonoNuclear Cells from patients with MS and control subjects under control conditions and in the presence of Interferon-ß-1b, RA, and the two combined.

Participants
Seventeen patients with Secondary/Progressive MS and 25 control subjects in a university hospital MS Clinic.

Results
Interferon-ß-1b use increased Interferon gamma-secreting cell counts, augmented T-Suppressor cell function, and inhibited T-Cell proliferation.

Therapy with RA decreased Interferon gamma-secreting cell counts, had a minimal positive effect on T-Suppressor cell function, and had no effect on T-Cell proliferation.

When RA and Interferon-ß-1b were combined, the inhibitory effect of RA on Interferon gamma-secreting cells predominated, T-Suppressor cell function increased synergistically over the increment observed with Interferon-ß-1b use alone, and the inhibitory effect of Interferon-ß-1b alone on T-cell proliferation remained unchanged.

Conclusions
Treatment with Interferon-ß-1b partially restores defective T-Suppressor cell function in patients with MS. This potentially beneficial action is synergistically potentiated by RA.

Interferon-ß-1b increases the number of Interferon gamma-secreting cells in the circulation when treatment is initiated.

A similar increment in Interferon gamma-secreting cells is observed when Interferon beta-1b is added to cultural peripheral blood Mononuclear cells in vitro. This potentially deleterious action of Interferon-ß-1b is reversed by RA.

Interferon-ß-1b inhibits Lymphocyte proliferation modestly but reproducibly. This action of Interferon-ß-1b is unaltered by RA.

These data provide a rationale for a trial of combination treatment with Interferon-ß-1b and RA in patients with MS.



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