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Androstenediol regulates systemic resistance against lethal infections in mice

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Summary

We previously reported that subcutaneous injection of DHEA (5-androsten-3 β-ol-17-one, dehydroepiandrosterone) protected mice from lethal infection. This included both a lethal herpes virus type 2 encephalitis and a lethal systemic coxsackievirus B 4 (CB 4) infection. Androstenediol (5-andros-ten-3 β-17 β-diol, AED), a metabolic product of DHEA is up to 100×more effective in regulating systemic resistance against lethal infection with CB 4 than its precursor DHEA. Compared to DHEA, treatment with AED was markedly superior in protecting mice against virus induced myocardiopathy, pancreopathy, and mortality. In addition to its protective effect, AED but not DHEA, induced a 3–4 fold proliferation of the spleen and thymus in virus infected animals; this effect of AED was only seen above a certain threshold dose. Neither steroid, however, has shown any significant direct antiviral effect in vitro; similarly, virus tissues titers in vivo are not affected by the hormones. Additionally, both DHEA and AED protected against a lethal infection withEnterococcus faecalis. These observations demonstrate that the steroid hormones DHEA and AED provide a novel approach for prevention and protection of the host from a variety of infectious diseases.

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References

  1. 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 

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

    Google Scholar 

  3. Berliner DL, Gallegos AJ (1967) Transformation and conjugation of dehydroepian-drosterone by human skin. J Clin Endocrinol 27: 1214–1218

    Google Scholar 

  4. Berliner DL, Pasqualini JR, Gallegos AJ (1968) The formation of water soluble steroids by human skin. J Invest Dermatol 50: 220–224

    Google Scholar 

  5. Daynes RA, Araneo BA (1990) Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Eur J Immunol 19: 2319–2325

    Google Scholar 

  6. Daynes RA, Dudley DJ, Araneo BA (1990) Regulation of murine lymphokines production in vivo. II. Dehydroepiandrosterone is a natural enhancer of interleukin 3 synthesis by helper T cells. Eur J Immunol 20: 893–802

    Google Scholar 

  7. Faredin I, Toth I (1975) The metabolism of [4-14C] 5 androstene-3 β, 17 β-diol by normal human skin in vitro. Acta Med Acad Sci Hung 32: 139–152

    Google Scholar 

  8. Faredin I, Fazekas A, Toth I, Juslesz M (1969) Transformation in vitro of [4-14C] dehydroepiandrosterone into 7-oxygenated derivatives by the normal human male and female skin tissue. J Invest Dermatol 52: 357–61

    Google Scholar 

  9. Gavan TL (1979) Microbiology: space, equipment, materials, and techniques. In: Henry JB (ed) Clinical diagnosis and management by laboratory methods, vol 2. WB Saunders, Philadelphia, pp 1570–1571

    Google Scholar 

  10. Grossman CJ (1984) Regulation of the immune system by sex steroids. Endocrine Rev 5: 435–455

    Google Scholar 

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

    Google Scholar 

  12. Heffner JE, Milam M (1990) Inhibition of rabbit lung G6PD by DHEA augments oxidant injury. Am J Respir Cell Mol Biol 2: 257–261

    Google Scholar 

  13. Loria RM, Inge TH, Cook S, Szakal A, Regelson W (1988) Protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (DHEA). J Med Virol 26: 301–14

    Google Scholar 

  14. Loria RM, Regelson W, Padgett DA (1990) Immune response facilitation and resistance to virus and bacterial infections with dehydroepiandrosterone (DHEA). In: Kalimi M, Regelson W (ed) The biologic role of dehydroepiandrosterone (DHEA). W De Gruyter, Berlin, pp 107–130

    Google Scholar 

  15. Loria RM, Padgett DA, Inge TH, Cook SH, Regelson W, Pascua JR, Dalton HP (1989) Dehydroepiandrosterone as an immune up-regulator. Symp Pharm Roussel Uclaf 9: 24

    Google Scholar 

  16. Loria RM, Montgomery LB, Corey LA, Chinchilli V (1984) Influence of diabetes mellitus heredity on susceptibility of coxsackie virus B 4. Arch Virol 81: 251–262

    Google Scholar 

  17. Ott L (1988) An introduction to statistical methods and data analysis, 3rd edn. PWS, Boston

    Google Scholar 

  18. Rager-Zisman B, Allison AC (1973) Effects of immunosuppression on coxsackie B 3 virus infection in mice, and passive protection by circulating antibody. J Gen Virol 19: 339–351

    Google Scholar 

  19. Toth I, Faredin I (1983) Concentrations of androgens and C 19-steroids sulfates in the abdominal skin of healthy women and men. Acta Med Hung 42: 13–20

    Google Scholar 

  20. Woodruff JF, Woodruff JJ (1975) The effects of viral infection on the function of the immune system. In: Notkins AL (ed) Viral immunology and immunopathology. Academic Press, New York, pp 393–418

    Google Scholar 

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Authors and Affiliations

  1. Departments of Microbiology and Immunology and of Pathology, Medical College of Virginia, Virginia Commonwealth University, School of Basic Health Science and Medicine, Richmond, Virginia, USA

    R. M. Loria & D. A. Padgett

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  1. R. M. Loria
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  2. D. A. Padgett
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Loria, R.M., Padgett, D.A. Androstenediol regulates systemic resistance against lethal infections in mice. Archives of Virology 127, 103–115 (1992). https://doi.org/10.1007/BF01309578

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  • DOI: https://doi.org/10.1007/BF01309578

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