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The low-molecular weight dipeptide bestatin is a potent inhibitor of aminopeptidase N and has been demonstrated to have antitumor and immunomodulatory action. The effects of bestatin on the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes, and the percentage and the absolute count of T cell subsets (CD4+CD8+, CD4–CD8–, CD4+, CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the spleen and mesenteric lymph nodes, as well as the production of cytokines by Th1/Th2 lymphocytes were studied in cyclophosphamide-immunocompromised mice. Bestatin was administered at doses of 1 and 0.1 mg/kg five times at 48 h intervals or ten times at 24 h intervals, intraperitoneally. Immunosuppression was induced by a single injection of cyclophosphamide at a dose of 350 mg/kg. It was found that bestatin administered ten times at 24 h intervals at a dose of 1 mg/kg increased the total number of splenic lymphocytes (which was previously decreased by cyclophosphamide). Five and ten exposures to the investigated doses enhanced the suppressive effect of cyclophosphamide on the percentage and the absolute count of B lymphocytes in the spleen and mesenteric lymph nodes. However, the drug increased the percentage and the absolute count of T lymphocytes CD3+ with concomitant increase in both subpopulations of T lymphocytes CD4+ and CD8+ in peripheral lymphatic organs of cyclophosphamide-immunocompromised mice. This immunocorrecting effect of bestatin depended on the dosage and the number of subsequent doses applied. Bestatin decreased the concentration of interleukin 2 (IL-2), interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) (which was previously increased by cyclophosphamide), irrespective of the dosage and the number of subsequent doses applied.

central-european journal of immunology/central european journal of immunology

Experimental immunology Modulatory effects of bestatin on T and B lymphocyte subsets and the concentration of cytokines released by Th1/Th2 lymphocytes in cyclophosphamide-treated mice