Laszlo Denes

In Vitro Effects of Tp5 Analogs on E-Rosette Formation and Cell Division

AbstractThe effects of seventeen synthetic analogs of thymopentin (TP-5) have been studied in the active and azathioprine-inhibited E-rosette tests.Thymopentin was gradually shortened from the C terminus to peptides and single amino acids. Thymopoietin 32-34 (Arg-Lys-Asp-RGH-0205-TP-3) (II) and thymopoietin 32-35 (Arg-Lys-Asp-Val-RGH-0206-TP-4) (I) were the most active peptides.Dipeptide Arg-Lys produced significant stimulatory effect on azathioprine (ED75) inhibited E-receptor. Treatment of azathioprine (ED75-inhibited E-rosette forming cells (ERFC) with arginine or especially lysine increased the number of ERFC.Some of TP-4 analogs decreased further the number of ERFC decreased by azathioprine ED30. These “suppressive” peptides as well as TP-3 caused a partial arrest of K 562 cell proliferation up to 96 hours.Results suggest that TP-5 is not the smallest active fragment of thymopoietins, since peptides (TP-3 and TP-4) exhibit similar or higher T-cell membrane activation on E-receptor. Arginine, lysine, ...

Selective restoration of immunosuppressive effect of cytotoxic agents by thymopoietin fragments

SummarySwiss male mice were immunosuppressed by cyclophosphamide, cisplatinum, vincristine and methotrexate. The ability of the thymopoietin (TP) fragments TP-3, TP-4 and TP-5 to restore antibody production and phagocytosis was studied. Impaired antibody production after vincristine treatment was partially or totally restored by TP-3, TP-4 or TP-5. Only TP-3 or TP-5 interfered with the antibody-production-damaging effect of cisplatinum. The same effect of methotrexate could not be influenced by any of the TP fragments. The phagocytic capacity of peritoneal macrophages was reduced by vincristine, methotrexate and cyclophosphamide treatment. In this respect, TP-3 protected the function of macrophages against vincristine and cyclophosphamide treatment. TP-4 was active in the case of damage caused by vincristine and methotrexate, and TP-5 interfered with the phagocytosis-inhibiting effect of methotrexate. Each TP fragment seems to have a specific target orientation within the immune system. This also means that the proper TP fragment should always be chosen for combination therapy with various types of cytotoxic drugs.

The Effect of Tp-3 (Arg-Lys-Asp), Tp-4 (Arg-Lys-Asp-Val), and Tp-5 On the Metastatic Capacity of Intravenously Injected Lewis Lung Tumor Cells

The oligopeptides Arg-Lys-Asp (TP-3), Arg-Lys-Asp-Val (TP-4), and Arg-Lys-Asp-Val-Tyr (TP-5) considered as the active short fragments of thymopoietin were administered (lo mg/kg) to C57B1 mice 24 hours before the intravenous inoculation of Lewis lung tumor (LLT) cells. A substantial decrease in lung metastasis number was observed as a result of treatment with all of the three oligopeptides. TP-3, TP-4, and TP-5 treatment decreased the immunosuppressive activity of Cyclophosphamid (240 mg/kg) given 96 hours before the inoculation of LLT cells. After thymectomy, performed eight days before the LLT inoculation, only TP-3 treatment resulted in the decrease of Cyclophosphamid immunotoxicity. A stimulating effect of TP-3 on T helper cell activity is assumed. The oligopeptides TP-3, TP-4, and TP-5 are recommended for clinical trial in case of malignant tumors and immunodeficiency.