Skip to main content

Advertisement

SpringerLink
Log in

Asthma and Dehydroepiandrosterone (DHEA): Facts and Hypotheses

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Dehydroepiandrosterone (DHEA) is considered as an important immunomodulating and anti-inflammatory hormone. Despite the continuing interest in DHEA replacement therapy, our knowledge of its effects upon asthma is very limited. DHEA is able to reverse cytokine imbalances associated with asthma, may prevent and attenuate allergic inflammation in airways, and does not possess the undesirable side effects of glucocorticoids; therefore, it may be potentially applied in the treatment of asthma. The steroid-sparing effect observed with DHEA clinically could appear especially favorable in asthmatic patients receiving oral treatment and those inhaling high doses of glucocorticoids. In addition, DHEA and its analogs might prove useful in reversing relative glucocorticoids insensitivity in patients with corticosteroid-resistant asthma. In this review we have focused specifically on DHEA’s role in asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Parker, L.N. 1991. Control of adrenal androgen secretion. Endocrinol Metab Clin North Am 20: 401–421.

    CAS  PubMed  Google Scholar 

  2. Kroboth, P.D., F.S. Salek, A.L. Pittenger, and T.J. Fabian. 1999. Frye RF DHEA and DHEA-S: A review. J Clin Pharmacol 39: 327–348.

    Article  CAS  PubMed  Google Scholar 

  3. Meikle, A.W., R.W. Dorchuck, B.A. Araneo, J.D. Stringham, T.G. Evans, S.L. Spruance, and R.A. Daynes. 1992. The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells. J Steroid Biochem Mol Biol 42: 293–304.

    Article  CAS  PubMed  Google Scholar 

  4. Okabe, T., M. Haji, R. Takayanagi, M. Adachi, K. Imasaki, F. Kurimoto, T. Watanabe, and H. Nawata. 1995. Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes. J Clin Endocrinol Metab 80: 2993–2996.

    Article  CAS  PubMed  Google Scholar 

  5. Webb, S.J., T.E. Geoghegan, R.A. Prough, and K.K. Michael Miller. 2006. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab Rev 38: 89–116.

    Article  CAS  PubMed  Google Scholar 

  6. Reed, M.J., A. Purohit, L.W. Woo, S.P. Newman, and B.V. Potter. 2005. Steroid sulfatase: Molecular biology, regulation, and inhibition. Endocr Rev 26: 171–202.

    Article  CAS  PubMed  Google Scholar 

  7. Casson, P.R., R.N. Andersen, H.G. Herrod, F.B. Stentz, A.B. Straughn, G.E. Abraham, and J.E. Buster. 1993. Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women. Am J Obstet Gynecol 169: 1536–1539.

    CAS  PubMed  Google Scholar 

  8. Harding, G., Y.T. Mak, B. Evans, J. Cheung, D. MacDonald, and G. Hampson. 2006. The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: Potential steroid-sparing role for DHEA. Cytokine 36: 57–68.

    Article  CAS  PubMed  Google Scholar 

  9. Yu, C.K., Y.H. Liu, and C.L. Chen. 2002. Dehydroepiandrosterone attenuates allergic airway inflammation in Dermatophagoides farinae-sensitized mice. J Microbiol Immunol Infect 35: 199–202.

    CAS  PubMed  Google Scholar 

  10. Kasperska-Zajac, A., Z. Brzoza, and B. Rogala. 2008. Dehydroepiandrosterone and dehydroepiandrosterone sulphate in atopic allergy and chronic urticaria. Inflammation 31: 141–145.

    Article  CAS  PubMed  Google Scholar 

  11. Dillon, J.S. 2005. Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: Their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy 4: 377–385.

    Article  CAS  PubMed  Google Scholar 

  12. Umetsu, D.T., and R.H. DeKruyff. 2006. The regulation of allergy and asthma. Immunol Rev 212: 238–255.

    Article  CAS  PubMed  Google Scholar 

  13. Larché, M. 2007. Regulatory T cells in allergy and asthma. Chest 132: 1007–1014.

    Article  PubMed  CAS  Google Scholar 

  14. Cheng, G.F., and J. Tseng. 2000. Regulation of murine interleukin-10 production by dehydroepiandrosterone. J Interferon Cytokine Res 20: 471–478.

    Article  PubMed  Google Scholar 

  15. Lucas, J.A., S.A. Ahmed, M.L. Casey, and P.C. MacDonald. 1985. Prevention of autoantibody formation and prolonged survival in New Zealand black/New Zealand white F1 mice fed dehydroisoandrosterone. J Clin Invest 75: 2091–2093.

    Article  CAS  PubMed  Google Scholar 

  16. Lin, X.H., I.S. Choi, Y.A. Koh, and Y. Cui. 2009. Effects of combined bacille Calmette-Guérin and dehydroepiandrosterone treatment on established asthma in mice. Exp Lung Res 35: 250–261.

    Article  CAS  PubMed  Google Scholar 

  17. Daynes, R.A., D.J. Dudley, and B.A. Araneo. 1990. Regulation of murine lymphokine production in vivo: II. dehydroepiandrosterone is a natural enhancer of interleukin 2 synthesis by helper T cells. Eur J Immunol 20: 793–802.

    Article  CAS  PubMed  Google Scholar 

  18. Kim, H.R., S.Y. Ryu, H.S. Kim, et al. 1995. Administration of dehydroepiandrosterone reverses the immune suppression induced by high doses of antigen in mice. Immunol Invest 24: 583.

    Article  CAS  PubMed  Google Scholar 

  19. Suzuki, T., N. Suzuki, R.A. Daynes, and E.G. Engleman. 1991. Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin Immunol Immunopathol 61(2 Pt 1): 202–211.

    Article  CAS  PubMed  Google Scholar 

  20. Choi, I.S., Y. Cui, Y.A. Koh, H.C. Lee, Y.B. Cho, and Y.H. Won. 2008. Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Korean J Intern Med 23: 176–181.

    Article  CAS  PubMed  Google Scholar 

  21. Yu, C.K., B.C. Yang, H.Y. Lei, Y.C. Chen, Y.H. Liu, C.C. Chen, and C.W. Liu. 1999. Attenuation of house dust mite Dermatophagoides farinae-induced airway allergic responses in mice by dehydroepiandrosterone is correlated with down-regulation of TH2 response. Clin Exp Allergy 29: 414–422.

    Article  CAS  PubMed  Google Scholar 

  22. Tabata, N., H. Tagami, and T. Terui. 1997. Dehydroepiandrosterone may be one of the regulators of cytokine production in atopic dermatitis. Arch Dermatol Res 289: 410–414.

    Article  CAS  PubMed  Google Scholar 

  23. Young, D.G., G. Skibinski, A. Skibinska, J.I. Mason, and K. James. 2001. Preliminary studies on the effect of dehydroepiandrosterone (DHEA) on both constitutive and phytohaemagglutinin (PHA)-inducible IL-6 and IL-2 mRNA expression and cytokine production in human spleen mononuclear cell suspensions in vitro. Clin Exp Immunol 123: 28–35.

    Article  CAS  PubMed  Google Scholar 

  24. Moynihan, J.A., T.A. Callahan, S.P. Kelley, and L.M. Campbell. 1998. Adrenal hormone modulation of type 1 and type 2 cytokine production by spleen cells: Dexamethasone and dehydroepiandrosterone suppress interleukin-2, interleukin-4, and interferon-gamma production in vitro. Cell Immunol 184(1): 58–64.

    Article  CAS  PubMed  Google Scholar 

  25. Akbari, O., P. Stock, R.H. DeKruyff, and D.T. Umetsu. 2003. Role of regulatory T cells in allergy and asthma. Curr Opin Immunol 15: 627–633.

    Article  CAS  PubMed  Google Scholar 

  26. Auci, D., L. Kaler, S. Subramanian, Y. Huang, J. Frincke, C. Reading, and H. Offner. 2007. A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: Androstene hormones as regulators of regulatory T cells. Ann N Y Acad Sci 1110: 630–640.

    Article  CAS  PubMed  Google Scholar 

  27. Wu, M.F., H.L. Chang, and J. Tseng. 1997. Dehydroepiandrosterone induces the transforming growth factor-beta production by murine macrophages. Int J Tissue React 19: 141–148.

    CAS  PubMed  Google Scholar 

  28. Brightling, C., M. Berry, and Y. Amrani. 2008. Targeting TNF-alpha: A novel therapeutic approach for asthma. J Allergy Clin Immunol 121: 5–10.

    Article  CAS  PubMed  Google Scholar 

  29. Di Santo, E., M. Sironi, T. Mennini, M. Zinetti, G. Savoldi, D. Di Lorenzo, and P. Ghezzi. 1996. A glucocorticoid receptor-independent mechanism for neurosteroid inhibition of tumor necrosis factor production. Eur J Pharmacol 299: 179–186.

    Article  PubMed  Google Scholar 

  30. Weinstein, R.E., C.A. Lobocki, S. Gravett, H. Hum, R. Negrich, J. Herbst, D. Greenberg, and D.R. Pieper. 1996. Decreased adrenal sex steroid levels in the absence of glucocorticoid suppression in postmenopausal asthmatic women. J Allergy Clin Immunol 97(1 Pt 1): 1–8.

    Article  CAS  PubMed  Google Scholar 

  31. Fehér, K.G., E. Koó, and T. Fehér. 1983. Adrenocortical function in bronchial asthma. Acta Med Hung 40(2–3): 125–131.

    PubMed  Google Scholar 

  32. Dunn, P.J., C.B. Mahood, J.F. Speed, and D.R. Jury. 1984. Dehydroepiandrosterone sulphate concentrations in asthmatic patients: Pilot study. NZ Med 28: 805–808.

    Google Scholar 

  33. Kannisto, S., M. Korppi, K. Remes, and R. Voutilainen. 2001. Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab 86: 4908–4912.

    Article  CAS  PubMed  Google Scholar 

  34. Dorsey, M.J., L.E. Cohen, W. Phipatanakul, D. Denufrio, and L.C. Schneider. 2006. Assessment of adrenal suppression in children with asthma treated with inhaled corticosteroids: Use of dehydroepiandrosterone sulfate as a screening test. Ann Allergy Asthma Immunol 97: 182–186.

    Article  CAS  PubMed  Google Scholar 

  35. Littley, M.D., A. Pollock, J. Kane, and S.M. Shalet. 1990. Basal serum dehydroepiandrosterone sulphate concentration does not predict the cortisol response to provocative testing. Ann Clin Biochem 27(Pt 6): 557–561.

    PubMed  Google Scholar 

  36. Dashtaki, R., A.R. Whorton, T.M. Murphy, P. Chitano, W. Reed, and T.P. Kennedy. 1998. Dehydroepiandrosterone and analogs inhibit DNA binding of AP-1 and airway smooth muscle proliferation. J Pharmacol Exp Ther 285: 876–883.

    CAS  PubMed  Google Scholar 

  37. Blauer, K.L., M. Poth, W.M. Rogers, and E.W. Bernton. 1991. Dehydroepiandrosterone antagonizes the suppressive effects of dexamethasone on lymphocyte proliferation. Endocrinology 129: 3174–3179.

    Article  CAS  PubMed  Google Scholar 

  38. Adcock, I.M., S.J. Lane, C.R. Brown, T.H. Lee, and P.J. Barnes. 1995. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med 182: 1951–1958.

    Article  CAS  PubMed  Google Scholar 

  39. Kasperska-Zajac, A.E., Z.K. Brzoza, E. Koczy-Baron, and J. Jagodzinska. 2009. Dehydroepiandrosterone in therapy of allergic diseases. Recent Pat Inflamm Allergy Drug Discov 3: 211–213.

    Article  CAS  PubMed  Google Scholar 

  40. Du, C., Q. Guan, M.W. Khalil, and S. Sriram. 2001. Stimulation of Th2 response by high doses of dehydroepiandrosterone in KLH-primed splenocytes. Exp Biol Med (Maywood) 226: 1051–1060.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Department of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia, ul. Ceglana 35, 40-925, Katowice, Poland

    Alicja Kasperska-Zajac

Authors
  1. Alicja Kasperska-Zajac
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alicja Kasperska-Zajac.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kasperska-Zajac, A. Asthma and Dehydroepiandrosterone (DHEA): Facts and Hypotheses. Inflammation 33, 320–324 (2010). https://doi.org/10.1007/s10753-010-9188-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-010-9188-1

KEY WORDS

Search

Navigation