Therapeutic possibilities of thymopoietin fragments (TP3 and TP4) based on experimental animal models.
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 Lyt 1+ cells, but the number of Lyt2+ increased in bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D007111:Immunity, Cellular / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013946:Thymopoietins / Q000494:pharmacology* / Q000627:therapeutic use; D013951:Thymus Hormones / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D009842:Oligopeptides; D010446:Peptide Fragments; D013946:Thymopoietins; D013951:Thymus Hormones; C051920:splenotritin; C045802:thymocartin