ALL-TRANS-RETINOIC ACID POTENTIATES THE ABILITY OF INTERFERON BETA-1BTO AUGMENT SUPPRESSOR-CELL FUNCTION IN MULTIPLE-SCLEROSIS

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.