Immunosuppressive effects of isoprinosine in man: a comparison to chlorambucil effects in multiple sclerosis.

Immunological and clinical functions were studied over a 2 year period in conjunction with a placebo controlled trial of isoprinosine and chlorambucil in 21 patients with exacerbating remitting multiple sclerosis. Laboratory and clinical evaluations were performed at 3 month intervals and during relapses. In placebo-treated patients, the decrease in circulating T8+ cells was maximum during relapses, T lymphocyte function was impaired, and five of the six patients experienced clinical worsening. Chlorambucil treatment was responsible for a decrease in circulating T4+ and T8+ cells; nevertheless, T lymphocyte function was slightly improved during relapses. The alterations of delayed hypersensitivity responses were not accompanied by improvement in relapse rate or in intensity and major side effects: mainly infections with leukopenia and thrombocytopenia. During isoprinosine therapy, a regulation of circulating T lymphocytes and cell proliferation occurred. The higher level of circulating T cells was related to the increase in T4+ and T8+ cells, which did not decrease during relapses. The absence of Leu 7+ cell modifications suggest that NK were numerically unaffected by isoprinosine therapy and that in vivo regulation of circulating T suppressor cells was performed by this treatment. Four out of seven patients did not experience any relapse during the duration of the trial. In relapsing patients, the frequency and duration of the relapses were significantly different from that of other patients. A reduction of the disease progression was observed without any side effects. While no conclusion can be drawn on the long-term effectiveness, the results of this pilot study are consistent indicators of the immunological and clinical beneficial effects of isoprinosine therapy in patients with exacerbating remitting multiple sclerosis.