Therapeutic possibilities of thymopoietin fragments (TP3 and TP4) based on experimental animal models

L. Denes, B. Szende, G. Y. Hajos, L. Szporny, K. Lapis

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The effects of thymic hormones are focused on the induction of T-cell subpopulations and restoration of the reactivity of an impaired immune system. TP3 and TP4 (corresponding to thymopoietin 32-34 and 32-35) exert a thymic hormone substitution effect. These peptides elicit dissimilar quantitative and qualitative effects. The aim of the present experiments was to investigate: (a) the effect of thymopoietin fragments in mice with unbalanced immune systems caused by experimental manipulation; and (b) the ratio of target cells after treatment. The distribution of Thy1, Lyt1, Lyt2 positivity was determined in a direct complement mediated cytotoxicity test. Autoantibody production was measured by Coombs' test. A count of Lewis Lung Tumour (LLT) metastases was made after two weeks of inoculation. Groups of mice were thymectomized and/or injected with cyclophosphamide (CY) (240 mg/kg) 96 h before tumour cell inoculation. The number of LLT metastases was decreased by treatment with peptides (TP3 = 72, TP4 = 97, TP5[thymopoietin 32-36] = 83.1 in %) and immunosuppression produced by CY was partly restored. After thymectomy, however, only TP3 treatment caused a decreasing effect (97.4%) on CY immunotoxicity independently of thymectomy. Inhibition of autoantibody production was detected with TP3 (5-6 weeks earlier than in mice treated with TP5). The ratio of Thy1+ and Lyt2+ cells was increased by treatment with TP3 and TP4, but the ratio of Lyt1+ cells was decreased by application of TP5. After TP3 treatment of nude mice the Lyt1+/Lyt2+ ratio increased both in bone marrow and spleen. No effect of TP4 was observed on Lyt1+ cells, but the number of Lyt2+ increased in bone marrow. TP3 and TP4 are rather small and active fragments of thymopoietin. Since they act on different targets, their therapeutic indications may be distinguished. It is supposed that TP3 produces an effect on the helper type and TP4 acts on the suppressive type of cells. The oligopeptides are recommended for clinical use in cases of malignant tumours (TP3) and immunodeficiency (TP4).

Original languageEnglish
Pages (from-to)279-287
Number of pages9
JournalDrugs under Experimental and Clinical Research
Volume13
Issue number5
Publication statusPublished - Oct 29 1987

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)

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