Abstract
We found that both thymosin from calf thymus and its constituent peptide α1 prepared by chemical synthesis restore cell-mediated immunity following its suppression in mice by injection of 5-FU. Conditions suitable for assessing the thymosin activity by means of footpad reaction were established in such immunosuppressed mice. In this new animal model, thymosin α1-peptide showed activity at a low dose of 5–50 μg/kg, which was 100–1,000 times less than that required for thymosin F-5 preparations.
Further studies utilizing the adoptive transfer technique showed that α1-peptide corrects the 5-FU-induced suppression of mature T cells, transferring the DTH response as well as that of macrophage function responsible for the expression of footpad reaction. Furthermore, regeneration of lymph node and bone marrow cells as well as CFU-c (progenitor cells of macrophages and granulocytes) was enhanced by thymosin α1 in the 5-FU-treated mice. All these results indicate that thymosin α1 accelerates the replenishment and maturation of haematopoietic cells, including not only T cells but also macrophages, when they have been severely damaged by the 5-FU treatment.
Keywords: Peptide, Lymph Node, Bone Marrow, Progenitor Cell, Bone Marrow Cell
References
- 1.Bach J-F. Thymic hormones. J Immunopharmacol. 1979;1:277. doi: 10.3109/08923977909026377. [DOI] [PubMed] [Google Scholar]
- 2.Bach J-F, Dardenne M, Pleau JM, Bach MA. Isolation, biochemical characteristics, and biological activity of a circulating thymic hormone in the mouse and in the human. Ann NY Acad Sci. 1975;249:186. doi: 10.1111/j.1749-6632.1975.tb29068.x. [DOI] [PubMed] [Google Scholar]
- 3.Bradley TR, Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966;44:287. doi: 10.1038/icb.1966.28. [DOI] [PubMed] [Google Scholar]
- 4.Chretien PB, Lipson SD, Cohen MH, Makuch R. Effect of thymosin in cancer patient: in vitro and in vivo studies. Proc Int Congr Pharmacol. 1978;7(2):263. [Google Scholar]
- 5.Goldstein AL, Banerjee S, Schneebeli GL, Dougherty TF, White A. Acceleration of lymphoid tissue regeneration in X-irradiated CBA/W mice by injection of thymosin. Radiat Res. 1970;41:579. [PubMed] [Google Scholar]
- 6.Goldstein AL, Guha A, Katz MM, Hardy MA, White A. Purification and biological activity of thymosin, a hormone of the thymus gland. Proc Natl Acad Sci USA. 1972;69:1800. doi: 10.1073/pnas.69.7.1800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Goldstein G. Isolation of bovine thymin: a polypeptide hormone of the thymus. Nature. 1974;247:11. doi: 10.1038/247011a0. [DOI] [PubMed] [Google Scholar]
- 8.Hooper JA, McDaniel MC, Thurman GB, Cohen GH, Schlof RS, Goldstein AL. The purification and properties of bovine thymosin. Ann NY Acad Sci. 1975;249:125. doi: 10.1111/j.1749-6632.1975.tb29063.x. [DOI] [PubMed] [Google Scholar]
- 9.Kenady DE, Chretien PB, Potrin C, Simon RM, Alexander JC, Jr, Goldstein AL. Effect of thymosin in vitro on T cell levels during radiation therapy. Correlation with radiation portal and initial T cell levels. Cancer. 1977;39:642. doi: 10.1002/1097-0142(197702)39:2<642::aid-cncr2820390241>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- 10.Martinez D, Field AK, Schwam H, Tytell AA, Hilleman MR. Failure of thymopoietin, ubiquitin and synthetic serum thymic factor to restore immunocompetence in T cell deficient mice (40313) Proc Soc Exp Biol Med. 1978;159:195. doi: 10.3181/00379727-159-40313. [DOI] [PubMed] [Google Scholar]
- 11.Ohta Y, Sueki K, Kitta K, Takemoto K, Ishitsuka H, Yagi Y. Comparative studies on the immunosuppressive effect among 5′-deoxy-5-fluorouridine, Fturafur and 5-fluorouracil. Gann. 1980;71:190. [PubMed] [Google Scholar]
- 12.Okuda S, Taniguchi K, Kubo C, Nomoto K. Effects of Corynebacterium parvum on depressed immunological reactions in animal models. Cancer Immunol Immunother. 1981;11:17. [Google Scholar]
- 13.Primus FJ, Demartino L, MacDonald R, Hanson HJ. Immunological reconstitution of T cell-deprived mice. I. Inability of thymosin to restore spleen cell mitogen and tumor allograft response. Cell Immunol. 1978;35:25. doi: 10.1016/0008-8749(78)90123-5. [DOI] [PubMed] [Google Scholar]
- 14.Trainin N, Small M. Studies on some physicochemical properties of a thymus humoral factor conferring immunocompetence on lymphoid cells. J Exp Med. 1970;132:885. doi: 10.1084/jem.132.5.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Umeda Y, Nakamura J, Ishitsuka H, Yagi Y (1982a) Protective activity of thymosin against opportunistic infections in animal models. Cancer Immunol Immunother [DOI] [PMC free article] [PubMed]
- 16.Umeda Y, Nakamura J, Sakamoto A, Ishitsuka H, Yagi Y (1982b) Protective activity of thymosin α1 against progression of tumor growth in mice immunosuppressed by cytostatic agent. Cancer Immunol Immunother [DOI] [PMC free article] [PubMed]
- 17.Wara DW, Goldstein AL, Doyle W, Amman AF. Thymosin activity in patients with cellular immunodeficiency. N Engl J Med. 1975;292:70. doi: 10.1056/NEJM197501092920204. [DOI] [PubMed] [Google Scholar]