Effects of isoprinosine in animal models of depressed T-cell function.

Isoprinosine--a new drug possessing immunostimulating properties--was investigated for its ability to influence cell-mediated immune responsiveness in animal models of deficient T-cell function. In vitro isoprinosine strongly increased T-cell mitogenesis in spleen cells from normal rats, with only modest increases in B-cell mitogenesis and no effects on unstimulated cells. In vivo isoprinosine (50 mg kg-1 day-1 orally) had no effects on spleen cell responsiveness when administered to normal rats for 4 or 14 days. However, when the same dose of isoprinosine was administered to rats immunosuppressed with cyclophosphamide (5 mg kg-1 day-1 orally) a partial restoration of T-cell mitogenesis was observed after 14 days of treatment. In rats with adjuvant arthritis treated with isoprinosine for 14 days, depressed T-cell responsiveness was completely restored to the level of the nonarthritic animals. The involvement of different cell types in the observed effects of isoprinosine was further studied in arthritic rats. Removal of monocytes/macrophages from the cell suspensions prior to culture did not affect the increased T-cell response in isoprinosine-treated rats, suggesting a direct stimulatory effect of isoprinosine on T-cell functions. T-suppressor cell function, impaired in arthritic rats, was not restored by treatment with isoprinosine. These results suggest that isoprinosine may exert selective effects on specific T-cell subsets, a finding that may increase the therapeutic interest of the drug.