RESTORATION OF IMPAIRED IMMUNE FUNCTIONS OF AGED ANIMALS BY CHRONIC BESTATIN TREATMENT

Abstract

An attempt to correct the immunodeficiency state in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 mo. old (C57B1/6 .times. BALB/c) F1 mice. Aged mice had depressed T [thymus-derived] cell and B[bone marrow-derived]-cell responses but increased ADCC [antibody-dependent cell-mediated cytotoxicity] activity. Weekly bestatin injections over 6 mo. resulted in varying effects depending on the dose administered. Small doses (10 .mu.g/injection) were more effective in restoring humoral responses to SRBC [sheep red blood cells] rather than delayed type hypersensitivity reactions, whereas large doses (100 .mu.g/injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent appearance of suppressor cells induced by aging. It led to significant ADCC activity reduction in aged animals near to the base line value of young animals. Animals were examined for presence of spontaneous tumors from the end of the treatment until the age of 28 mo. Significant spontaneous tumor incidence reduction was observed in mice given repeated 100 .mu.g bestatin injections when compared to untreated aged mice and to mice given low bestatin doses.