Correction of immunodeficiency in aged mice by levamisole and bestatin administration.

Abstract

An attempt to correct the impaired immune functions of aged mice was made by injecting repeatedly (over a 6-month period) two chemically defined immunostimulating agents, levamisole and bestatin, into 12- to 16-month-old hybrid mice. Continuous treatment with levamisole restored T-cell-dependent functions (delayed-type hypersensitivity reaction and antibody response to T-dependent antigens) and prevented the appearance of suppressor cells induced by aging. In aged animals, this treatment led to macrophage activation and to a significant reduction of ADCC activity near the baseline value of young animals. Weekly injections of bestatin resulted in varying effects, depending on the dose administered. Small doses (10 microgram/injection) were more effective in restoring humoral response to SRBC rather than delayed-type hypersensitivity reaction, whereas large doses (100 microgram/injection) had the opposite effect. Macrophage activation was obtained only after the administration of the high dose of bestatin. Continuous treatment with bestatin did not eliminate suppressor cell activity, but decreased the ADCC normally elevated in aged animals. A significant reduction of spontaneous tumors and prolongation of median survival was observed in mice given repeated injections of levamisole and of 100 microgram bestatin, compared with untreated aged mice and with mice given low doses of bestatin.