Hostname: page-component-7c8c6479df-nwzlb Total loading time: 0 Render date: 2024-03-28T21:44:08.568Z Has data issue: false hasContentIssue false

Action of cyclosporin A on the tapeworm Hymenolepis diminuta in mice

Published online by Cambridge University Press:  06 April 2009

J. M. Wastling
Affiliation:
Department of Zoology, University of Aberdeen, Tillydrone Avenue, Aberdeen AB9 2TN, Scotland
D. Gerrard
Affiliation:
Department of Zoology, University of Aberdeen, Tillydrone Avenue, Aberdeen AB9 2TN, Scotland
J. Walker
Affiliation:
Department of Zoology, University of Aberdeen, Tillydrone Avenue, Aberdeen AB9 2TN, Scotland
L. H. Chappell
Affiliation:
Department of Zoology, University of Aberdeen, Tillydrone Avenue, Aberdeen AB9 2TN, Scotland

Summary

Cyclosporin A (CsA), administered in 5 daily subcutaneous doses of 50 mg/kg to MF1 mice immediately following infection with Hymenolepis diminuta enhanced parasite growth relative to controls. Drug administered at 24 h intervals for 10 days, and thereafter every 48 h to MF1 and CBA/Ca mice infected with H. diminuta, increased worm survival and growth, delayed host-mediated expulsion of the parasite and enabled some worms to develop to patency. Worm survival and weight both increased in a dose-dependent manner following daily CsA treatment of infected CBA/Ca and BALB/c mice (0–150 mg/kg CsA/day). Delay in parasite elimination was accompanied by increased frequency of worm-attachment in the anterior small intestine (MF1 mice given 5 daily doses of CsA [0–150 mg/kg] following infection); posteriad migration of worms was restricted in a dose-dependent manner. The data presented contrast markedly with the action of the same drug on H. microstoma in mice. Thus CsA treatment acts in opposing ways on two closely related parasites in the same host; this possibly reflects the mechanistic antagonism between immunosuppression and anthelmintic activity. This paper reports the first use of a specific T cell-suppressive drug on H. diminuta in the mouse, implicating the role of T cells in protective immunity to this parasite.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1990

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Belosevic, M., Faubert, G. M. & Maclean, J. D. (1986). The effects of cyclosporin A on the course of infection with Giardia muris in mice. American Journal of Tropical Medicine and Hygiene 35, 496500.CrossRefGoogle ScholarPubMed
Beveridge, T. (1982). Pharmacokinetics and metabolism of Cyclosporin A. In Cyclosporin A, Proceedings of an International Conference on Cyclosporin A (ed. White, D. J. G.), pp. 3544. Amsterdam: Elsevier Biomedical Press.Google Scholar
Bland, P. W. (1976). Immunity to Hymenolepis diminuta: unresponsiveness of the athymic nude mouse to infection. Parasitology 72, 93–7.CrossRefGoogle ScholarPubMed
Bolas-Fernandez, F., Grencis, R. K. & Wakelin, D. (1988). Cyclosporin A and Trichinella spiralis: anthelmintic effects in immunosuppressed mice. Parasite Immunology 10, 111–16.CrossRefGoogle ScholarPubMed
Chappell, L. H. & Thompson, A. W. (1988). Studies on the action of Cyclosporin A against Schistosoma mansoni and other parasitic infections. Transplantation Proceedings 20, 291–7.Google ScholarPubMed
Chappell, L. H., Thomson, A. W., Barker, G. C. & Smith, S. W. G. (1987). Dosage, timing, and route of administration of Cyclosporin A and non-immunosuppressive derivatives of dihydrocyclosporin A and Cyclosporin C against Schistosoma mansoni in vivo and in vitro. Antimicrobial Agents and Chemotherapy 31, 1567–71.CrossRefGoogle Scholar
Chappell, L. H., Wastling, J. M. & Hurd, H. (1989). Action of cyclosporin A on the tapeworms Hymenolepis microstoma, H. diminuta and Mesocestoides corti in vivo. Parasitology 98, 291–9.CrossRefGoogle ScholarPubMed
Choromanski, L. (1983). Experimental infections of rats and mice with Hymenolepis diminuta (Cestoda, Hymenolepididae), and influence of immunosuppression on the infection in mice. Acta Parasitologica Polonica 28, 317–26.Google Scholar
Hashiguchi, Y. & Okamura, Y. (1988). The effect of cyclosporin A on the course of Paragonimus miyazakii infection in rats. Journal of Helminthology 62, 251–6.CrossRefGoogle ScholarPubMed
Hopkins, C. A. (1980). Immunity and Hymenolepis diminuta. In Biology of the Tapeworm Hymenolepis diminuta (ed. Arai, H. P.), pp. 551614. London: Academic Press.CrossRefGoogle Scholar
Hopkins, C. A., Subramanian, G. & Stallard, H. (1972 a). The development of Hymenolepis diminuta in primary and secondary infections in mice. Parasitology 64, 401–12.CrossRefGoogle ScholarPubMed
Hopkins, C. A., Subramanian, G. & Stallard, H. (1972 b). The effect of immunosuppressants on the development of Hymenolepis diminuta in mice. Parasitology 65, 111–20.CrossRefGoogle ScholarPubMed
Hughes, W. T. & Smith, B. (1982). Provocation of infection due to Pneumocystis carinii by cyclosporin A. Journal of Infectious Diseases 145, 767.CrossRefGoogle ScholarPubMed
Issak, D. A., Jacobson, R. H. & Reed, N. D. (1975). Thymus dependence of tapeworm (Hymenolepis diminuta) elimination from mice. Infection and Immunity 12, 1478–9.CrossRefGoogle Scholar
Kierszenbaum, F., Gottlieb, C. A. & Budzko, D. B. (1983). Exacerbation of Trypanosoma cruzi infection in mice treated with the immunoregulatory agent cyclosporin A. Tropenmedizin und Parasitologie, 34, 46.Google ScholarPubMed
Mccabe, R. E., Remington, J. S. & Araujo, F. G. (1985). In vivo and in vitro effects of Cyclosporin A on Trypanosoma cruzi. American Journal of Tropical Medicine and Hygiene 34, 861–5.CrossRefGoogle ScholarPubMed
Mody, C. H., Toews, G. B. & Lipscomb, M. F. (1988). Cyclosporin A inhibits the growth of Cryptococcus neoformans in a murine model. Infection and Immunity 56, 712.CrossRefGoogle ScholarPubMed
Munro, G. H. & Mclaren, D. J. (1990). Schistosoma mansoni: morphology and ultrastructure of adult worms recovered from cyclosporin-A treated mice. Parasitology 100, 1928.CrossRefGoogle ScholarPubMed
Ryffel, B. (1982). Experimental toxicological studies with Cyclosporin A. In Cyclosporin A, Proceedings of an International Conference on Cyclosporin A (ed. White, D. J. G.), pp. 4575. Amsterdam: Elsevier Biomedical Press.Google Scholar
Thomson, A. W. & Duncan, J. I. (1989). The influence of cyclosporin A on T cell activation, cytokine gene expression and cell-mediated immunity. In Cyclosporin, Mode of Action and Clinical Applications (ed. Thomson, A. W.), pp. 5081. Lancaster (UK): Kluwer Academic Publishers.Google Scholar
Thomson, A. W., Moon, D. K. & Nelson, D. S. (1983). Suppression of delayed-type hypersensitivity reactions and lymphokine production by cyclosporin A in the mouse. Clinical and Experimental Immunology 52, 599606.Google ScholarPubMed