Immunomodulation induced by Ubenimex, and antibiotic inhibitor of aminopeptidase

Mice were treated with Ubenimex, which is clinically used as an immunopoten tiator for patients with acute myelogenic leukemia, to examine how this dru g modulates the immune system. Ubenimex (0.1 or 1.0 mg/day/mouse) was orall y administered for a week and the phenotype of leukocytes in the liver, spl een, thymus, and bone marrow was analyzed by immunofluorescence tests. The proportion and number of extrathymic T cells (i.e., IL-2R beta(+)CD3(int)) and NK cells (i.e, IL-2 beta(+)CD3(-)) increased in the liver, while those of granulocytes (i.e., Mac-1(+)Gr-1(+)) increased in the bone marrow of mic e treated with Ubenimex. In parallel with this numerical increase, the cyto toxicity of extrathymic T cells and NK cells in the liver and the level of Ca2+ influx from granulocytes in the bone marrow were also augmented. These results help elucidate the mechanisms underlying the immunopotentiation as cribed to Ubenimex.