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Herpes simplex virus infection and damage in the central nervous system: immunomodulation with adjuvant, cyclophosphamide and cyclosporin A

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Summary

The role of the immune system in damage to the central nervous system (CNS) following infection with herpes simplex virus (HSV) was studied with the use of immune adjuvants and immunosuppressive drugs. The incidence of paralysis was found to be influenced significantly by the immune status of the animal. Thus, cyclosporin A (CsA) reduced the incidence of ear paralysis following inoculation of the pinna with virus, whilst cyclophosphamide (CY) increased the incidence of hind limb paralysis following i.v. inoculation with virus. Non-specific immunopotentiation with complete Freund's adjuvant (CFA) increased the incidence of hind limb paralysis. The inclusion of CNS antigen (mouse spinal cord homogenate) with the adjuvant enhanced the effect of adjuvant alone. The findings suggest that regulation of the immune response in the CNS may be of importance in the control of HSV-induced neuropathology.

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References

  1. Altmann DM, Blyth WA (1985) The effects of cyclosporin A on the induction, expression and regulation of the immune response to herpes simplex virus. Clin Exp Immunol 59: 17–22

    Google Scholar 

  2. Balow JE, Parrillo JE, Fauci AS (1977) Characterization of the direct effects of cyclophosphamide on cell-meediated immunological responses. Immunology 32: 899–904

    Google Scholar 

  3. Bishop SA, Hill TJ (1989) Herpes simplex virus infection and damage in the central nervous system: immune response to myelin basic protein. J Neurol Sci 91: 109–118

    Google Scholar 

  4. Borel JF, Feurer C, Magnee C, Stahelin H (1977) Effects of the new anti-lymphocytic peptide, cyclosporin A, in animals. Immunology 32: 1017–1025

    Google Scholar 

  5. Caspary EA (1977) Effect of live attenuated vaccines on the course of experimental allergic encephalitis. Eur Neurol 16: 176–180

    Google Scholar 

  6. Cohen IR (1985) Experimental autoimmune encephalitis: Pathogenesis and prevention. In: Vandenbark AA (ed) Immuno-regulatory processes in multiple sclerosis and experimental allergic encephalitis. Elsevier, Amsterdam, pp 1–54

    Google Scholar 

  7. Dubbs Dr, Kitt S (1964) Mutant strains of herpes simplex deficient in thymidine kinase-inducing activity. Virology 22: 493–502

    Google Scholar 

  8. Hill TJ (1983) Herpesviruses in the central nervous system. In: Mims CA (ed) Viruses and demyelinating diseases. Academic Press, New York, pp 29–45

    Google Scholar 

  9. Hill TJ, Field HJ, Blyth WA (1975) Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J Gen Virol 28: 341–353

    Google Scholar 

  10. Hill TJ, Yirrell DL, Blyth WA (1986) Infection of the adrenal gland as a route to the central nervous system after viraemia with herpes simplex virus in the mouse. J Gen Virol 67: 305–320

    Google Scholar 

  11. Hutchinson IF, Shadur CA, Duarte JSA, Strom TB, Tilney NL (1981) Cyclosporin A spares selectively lymphocytes with donor specific suppressor characteristics. Transplantation 32: 210–216

    Google Scholar 

  12. Kristensson K (1978) Retrograde transport of macromolecules in axons. Annu Rev Pharmacol Toxicol 18: 97–110

    Google Scholar 

  13. Kristensson K, Svennerholm B, Persson L, Vahlne A, Lycke E (1979) Latent herpes simplex virus trigeminal ganglionic infection in mice and demyelination in the central nervous system. J Neurol Sci 43: 253–264

    Google Scholar 

  14. Kristensson K, Svennerholm B, Lycke E (1983) Herpes simplex virus-induced demyelination. Effects of reinfection and challenge with neuroantigens. J Neurol Sci 60: 247–252

    Google Scholar 

  15. Lando Z, Teitelbaum D, Arnon R (1979) Effect of cyclophosphamide on suppressor cell activity in mice unresponsive to EAE. J Immunol 123: 2156–2160

    Google Scholar 

  16. Lawman MJ, Rouse BT, Courtney RJ, Walker RD (1980) Cell-mediated immunity against simplex virus. Induction of cycotoxic T lymphocytes. Infect Immunol 27: 133–139

    Google Scholar 

  17. Leapman SB, Filo RS, Smith EJ, Smith PG (1980) In-vitro effects of cyclosporin A on lymphocyte sub-populations. 1. Suppressor cell sparing by cyclosporin A. Transplantation 30: 404–408

    Google Scholar 

  18. Levine S, Wenk EJ (1966) Exacerbation and transformation of allergic encephalomyelitis by pertussis vaccine. Proc Soc Exp Biol Med 122: 115–118

    Google Scholar 

  19. Massanari RM, Paterson PY, Lipton HL (1979) Potentiation of EAE in hamsters with persistent encephalitis due to measles virus. J Infect Dis 139: 279–303

    Google Scholar 

  20. Miyazaki C, Nakamura T, Kaneko K, Mori R, Shibasaki H (1985) Reinduction of experimental allergic encephalomyelitis in convalescent Lewis rats with cyclophosphamide. J Neurol Sci 67: 277–284

    Google Scholar 

  21. Moore GRW, Traugott U, Farooq M, Norton WT, Raine CS (1984) Experimental autoimmune encephalitis: augementation of demyelination by different myelin lipids. Lab Invest 51: 416–424

    Google Scholar 

  22. Morris PJ (1981) Cyclosporin A. Transplantation 32: 349–353

    Google Scholar 

  23. Nash AA, Leung K-N, Wildy P (1985) The T cell mediated immune response of mice to herpes simplex virus. In: Roizman B, Lopez C (eds) The herpesviruses, vol 4. Plenum Press, New York, pp 87–102

    Google Scholar 

  24. Raine CS, Traugott U, Farooq M, Bornstein MB, Norton WT (1981) Augmentation of immune-mediated demyelination by lipid haptens. Lab Invest 45: 174–182

    Google Scholar 

  25. Reiber H, Suckling AJ, Rumsby MG (1984) The effect of Freunds adjuvant on blood-cerebrospinal fluid barrier permeability. J Neurol Sci 63: 55–61

    Google Scholar 

  26. Reiber H, Suckling AJ (1986) Cyclosporin A treatment of experimental allergic encephalitis: changes in immunological regulation and blood-CSF barrier function. J Neuroimmunol 12: 121–130

    Google Scholar 

  27. Swierkosz JE, Swanborg RH (1977) Immunoregulation of experimental allergic encephalitis: conditions for induction of suppressor cells and analysis of mechanism. J Immunol 119: 1501–1506

    Google Scholar 

  28. Townsend JJ (1981) The demyelinating effect of corneal HSV infections in normal and nude (athymic) mice. J Neurol Sci 50: 435–441

    Google Scholar 

  29. Townsend JJ, Baringer JR (1978) Central nervous system susceptibility to herpes simplex infection. J Neuropathol Exp Neurol 63: 95–101

    Google Scholar 

  30. Townsend JJ, Baringer JR (1979) Morphology of central nervous system disease in immunosuppressed mice after peripheral herpes simplex virus inoculation. Lab Invest 40: 148–182

    Google Scholar 

  31. Turk JL, Parker D (1982) Effect of cyclophosphamide on immunological control mechanisms. Immunol Rev 65: 99–113

    Google Scholar 

  32. Wang BS, Heacock EH, Chang-xue Z, Tilney NL, Strom TB, Mannick JA (1982) Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin A. J Immunol 128: 1382–1385

    Google Scholar 

  33. White DJG, Plumb AM, Pawelec G, Brons G (1979) Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells. Transplantation 27: 55–58

    Google Scholar 

  34. Wildy P (1967) The progression of herpes simplex virus to the central nervous system of the mouse. J Hyg 65: 173–192

    Google Scholar 

  35. Wisniewski HM, Bloom BR (1975) Primary demyelination as a non-specific consequence of a cell-mediated immune reaction. J Exp Med 141: 346–359

    Google Scholar 

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Bishop, S.A., Hill, T.J. Herpes simplex virus infection and damage in the central nervous system: immunomodulation with adjuvant, cyclophosphamide and cyclosporin A. Archives of Virology 116, 57–68 (1991). https://doi.org/10.1007/BF01319231

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  • DOI: https://doi.org/10.1007/BF01319231

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