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Protective effects of melatonin in mice infected with encephalitis viruses

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Summary

We examined the effect of the pineal neurohormone melatonin (MLT) on protection from viral encephalitis. The antiviral activity of MLT was evaluated in normal mice inoculated with Semliki Forest virus (SFV) and in stressed mice injected with the attenuated non-invasive West Nile virus (WN-25). Administration of MLT (s.c.) daily from 3 days before through 10 days after virus inoculation reduced viremia and significantly postponed the onset of disease and death by 7 to 10 days. Moreover, MLT injection reduced mortality of SFV (10 PFU) inoculated mice from 100% to 44%. In mice inoculated with high dose of SFV (100 PFU), MLT postponed death and reduced mortality by 20%. In all of the surviving mice anti-SFV antibodies were detected 22 days after virus inoculation. Infection of mice stressed by either isolation or dexamethasone injection with WN-25 induced mortality of 75% and 50% respectively, which was reduced by MLT administration to 31% and 25%, respectively. The efficiency of MLT in protecting from lethal viral infections warrants further investigations on its mechanisms of action.

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References

  1. Ader R (ed) (1981) Psychoneuroimmunology. Academic Press, New York

    Google Scholar 

  2. Ben-Nathan D, Lustig S, Feuerstein G (1989) The influence of cold or isolation stress on neuroinvasiveness and virulence of an attenuated variant of West Nile virus. Arch Virol 109: 1–10

    Google Scholar 

  3. Ben-Nathan D, Feuerstein G (1990) The influence of cold or isolation stress on resistance of mice to West Nile virus encephalitis. Experientia 46: 285–290

    Google Scholar 

  4. Ben-Nathan D, Lustig S, Kobiler D, Danenberg HD, Lupu E, Feuerstein G (1992) Dehydroepiandrosterone (DHEA) protects mice inoculated with West Nile virus and exposed to cold stress. J Med Virol 38: 159–166

    Google Scholar 

  5. Ben-Nathan D, Kobiler D, Feuerstein G, Lustig S (1992) Anti-stress effect of dehydroepinadrosterone (DHEA) on mice inoculated with attenuated arboviruses. Progr Neuro Endocrin Immunol 5: 229–234

    Google Scholar 

  6. Ben-Nathan D, Lachmi B, Lustig S, Feuerstein G (1991) Protection of dehydroepiandrosterone (DHEA) in mice infected with viral encephalitis. Arch Virol 120: 263–271

    Google Scholar 

  7. Blalock JE (1987) Virus induced increase in plasma corticosterone. Science 238: 1424–1425

    Google Scholar 

  8. Bradish CJ, Allner K, Maber HB (1971) The virulence of original and derived strains of Semliki Forest virus for mice, guinea pigs and rabbits. J Gen Virol 12: 141–160

    Google Scholar 

  9. Bradish CJ, Allner K (1972) The early responses of mice of respiratory or intraperitoneal infection by defined virulent and avirulent strains of Semliki Forest virus. J Gen Virol 15: 205–218

    Google Scholar 

  10. Colombo, LL, Cheu, GJ, Lopez MC, Watson RR (1992) Melatonin induced increase in gamma-interferon production by murine splenocytes. Immunol Lett 33: 123–126

    Google Scholar 

  11. Dulbecco R, Vogt M (1956) Plaque formation and isolation of pure lines with poliomelitis viruses. J Exp Med 99: 167–182

    Google Scholar 

  12. Grimley PM, Friedman RM (1970) Arboviral infection of voluntary striated muscles. J Infect Dis 122: 45–52

    Google Scholar 

  13. Grossman CJ (1985) Interaction between the gonadal steroids and the immune system. Science 227: 257–260

    Google Scholar 

  14. Halevy M, Akov Y, Ben-Nathan D, Kobiler D, Lachmi B, Lustig S (1994) Loss of active neuroinvasiveness in attenuated strains of West Nile virus: pathogenicity in immunocompetent and SCID mice. Arch Virol 137: 355–370

    Google Scholar 

  15. Maestroni GJM, Conti A (1993) Melatonin in relation to the immune system. In: Melatonin. Biosynthesis, physiological effect, and clinical applications. Yu HS, Reiter RJ (eds) CRC Press, Boca Raton, pp 289–311

    Google Scholar 

  16. Maestroni GJM, Conti A, Pierpaoli W (1988) Pineal melatonin, its fundamental immunoregulatory role in aging and cancer. Ann NY Acad Sci 521: 140–148

    Google Scholar 

  17. Maestroni GJM, Conti A, Pierpaoli W (1988) Role of the pineal gland in immunity: III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism. Immunology 63: 465–469

    Google Scholar 

  18. Maestroni GJM, Conti A, Pierpaoli W (1987) The pineal gland and the circadian opiatergic, immunoregulatory role of melatonin. Ann NY Acad Sci 496: 67–77

    Google Scholar 

  19. Maestroni GJM, Conti A, Pierpaoli W (1987) Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism. Clin Exp Immunol 68: 384–391

    Google Scholar 

  20. Maestroni GJM, Conti A (1990) The pineal neurohormone melatonin stimulates activated CDL + Thy 1 + cells to release opioid agenist(s) with immunoenhancing and anti-stress properties. J Neuroimmunol 28: 167–176

    Google Scholar 

  21. Maestroni GJM, Conti A (1991) Role of the pineal neurohormone melatonin in the psycho-neuroendocrine-immune network. Psychoneuroimmunology, 2nd edn. Academic Press, San Diego, pp 495–513

    Google Scholar 

  22. Maestroni GJM, Conti A, Pierpaoli W (1986) Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonize the immunosuppressive effect of corticosterone. J Neuroimmunol 13: 19–30

    Google Scholar 

  23. Murphy FA, Haresson AK, Collin WK (1970) The role of extra-neural arbovirus infection in the pathogenesis of encephalitis: an electron microscopic study of Semliki Forest virus infection in mice. Lab Invest 22: 318–328

    Google Scholar 

  24. Musceltola M, Grasso G, Fanetti G, Tanganelli C, Borghesi-Nicolelti C (1992) Melatonin and modulation of interferon-gamma production. Neuropeptides 22: 46 [Abstract]

    Google Scholar 

  25. Rager-Zisman B, Allison AC (1973) The role of antibodies and host cells in the resistance of mice against infection by Coxsakie B3 virus. J Gen Virol 19: 329–338

    Google Scholar 

  26. Reed LG, Muench M (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27: 493–497

    Google Scholar 

  27. Reiter RJ (ed) (1984) The pineal gland. Raven Press, New York

    Google Scholar 

  28. Riley V (1981) Psychoneuroendocrine influence on immune competence and neoplasia. Science 212: 1100–1109

    Google Scholar 

  29. Smith EM, Mayer WJ, Blalock JE (1981) Virus-induced corticosterone in hypophysectomized mice; a possible lymphoid adrenal axis. Science 218: 1311–1312

    Google Scholar 

  30. Solomon GF (1987) Psychoneuroimmunology: interaction between central nervous system and immune system. J Neurosci Res 18: 1–9

    Google Scholar 

  31. Thong HY, Vincent MM, Hensen, SA, Fuccillo DA, Rola-Plesczynski M, Bellanti J (1975) Depressed specific cell mediated immunity to herpes simplex virus type 1 in patients with recurrent herpes labialis. Infect Immun 12: 76–80

    Google Scholar 

  32. Waldhauser F, Steger H (1986) Changes in melatonin secretion with age and pubescence. J Neural Transm [Suppl] 21: 183–199

    Google Scholar 

  33. Willems WR, Kaluza G, Boschek CB, Barrier H, Hager H, Schutz HJ, Feistner H (1979) Semliki Forest virus: cause of a fatal case of human encephalitis. Science 203: 1127–1129

    Google Scholar 

  34. Yirrell DL, Blyth WA, Hill TJ (1987) The influence of adrogens paralysis in mice following intravenous inoculation of herpes simplex virus. J Gen Virol 68: 2461–74

    Google Scholar 

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Authors and Affiliations

  1. Department of Virology, Israel Institute for Biological Research, Ness-Ziona, Israel

    D. Ben-Nathan & S. Lustig

  2. Center for Experimental Pathology, Istituto Cantonale di Patologia, Locarno, Switzerland

    G. J. M. Maestroni & A. Conti

Authors
  1. D. Ben-Nathan
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  2. G. J. M. Maestroni
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  3. S. Lustig
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  4. A. Conti
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Ben-Nathan, D., Maestroni, G.J.M., Lustig, S. et al. Protective effects of melatonin in mice infected with encephalitis viruses. Archives of Virology 140, 223–230 (1995). https://doi.org/10.1007/BF01309858

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  • DOI: https://doi.org/10.1007/BF01309858

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