Display options
Cite
Conrad D, Wang A, Pieters R, et al. HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. J Inflamm (Lond). 2010;7:52doi: 10.1186/1476-9255-7-52.
Conrad, D., Wang, A., Pieters, R., Nicoletti, F., Mangano, K., van Heeckeren, A. M., White, S. K., Frincke, J. M., Reading, C. L., Stickney, D., & Auci, D. L. (2010). HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. Journal of inflammation (London, England), 752. https://doi.org/10.1186/1476-9255-7-52
Conrad, Douglas, et al. "HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression." Journal of inflammation (London, England) vol. 7 (2010): 52. doi: https://doi.org/10.1186/1476-9255-7-52
Conrad D, Wang A, Pieters R, Nicoletti F, Mangano K, van Heeckeren AM, White SK, Frincke JM, Reading CL, Stickney D, Auci DL. HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. J Inflamm (Lond). 2010 Oct 30;7:52. doi: 10.1186/1476-9255-7-52. PMID: 21034489; PMCID: PMC2984480.
Copy Download .nbib Format: NLM
Share it on

J Inflamm (Lond). 2010 Oct 30;7:52. doi: 10.1186/1476-9255-7-52.

HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression.

Journal of inflammation (London, England)

Douglas Conrad, Angela Wang, Raymond Pieters, Ferdinando Nicoletti, Katia Mangano, Anna M van Heeckeren, Steven K White, James M Frincke, Christopher L Reading, Dwight Stickney, Dominick L Auci

Affiliations

  1. Harbor Biosciences, 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USA. [email protected].

PMID: 21034489 PMCID: PMC2984480 DOI: 10.1186/1476-9255-7-52

Abstract

BACKGROUND: 17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286) is a synthetic derivative of an endogenous steroid androstenetriol (β-AET), a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA), with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact.

METHODS AND RESULTS: In mice, oral treatment with HE3286 (40 mg/kg) significantly (p < 0.05) decreased neutrophil counts and exudate volumes (~50%) in carrageenan-induced pleurisy, and myeloperoxidase in lipopolysaccharide-induced lung injury. HE3286 (40 mg/kg) was not found to be profoundly immune suppressive in any of the classical animal models of immune function, including those used to evaluate antigen specific immune responses in vivo (ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged with K. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups.

CONCLUSIONS: HE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.

References

  1. Lancet. 1994 Jun 11;343(8911):1479-81 - PubMed
  2. Steroids. 2002 Nov;67(12):967-77 - PubMed
  3. Pulm Pharmacol Ther. 2006;19(3):155-65 - PubMed
  4. J Clin Endocrinol Metab. 2003 Sep;88(9):4293-302 - PubMed
  5. Am J Obstet Gynecol. 1992 Apr;166(4):1163-8; discussion 1168-70 - PubMed
  6. Cell Immunol. 2006 Jun;241(2):66-74 - PubMed
  7. Eur J Pharmacol. 2006 Mar 8;533(1-3):133-44 - PubMed
  8. Chest. 2004 Aug;126(2 Suppl):150S-158S; discussion 159S-161S - PubMed
  9. Clin Chest Med. 2007 Jun;28(2):331-46 - PubMed
  10. Pharmacol Rev. 2004 Dec;56(4):515-48 - PubMed
  11. Ann N Y Acad Sci. 1992 Apr 15;650:363-6 - PubMed
  12. Pulm Pharmacol Ther. 2000;13(2):61-9 - PubMed
  13. Biochem J. 2002 May 15;364(Pt 1):115-20 - PubMed
  14. Am J Physiol Endocrinol Metab. 2010 May;298(5):E1036-48 - PubMed
  15. J Steroid Biochem Mol Biol. 2006 Jul;100(1-3):42-51 - PubMed
  16. Infect Immun. 2001 Sep;69(9):5294-304 - PubMed
  17. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Feb 15;767(2):285-99 - PubMed
  18. J Immunol. 2007 Nov 15;179(10):7001-11 - PubMed
  19. J Invest Dermatol. 1969 Apr;52(4):357-61 - PubMed
  20. Diabetes Care. 2005 Sep;28(9):2141-4 - PubMed
  21. Med Sci Monit. 2007 Feb;13(2):RA19-24 - PubMed
  22. J Pharmacol Exp Ther. 2009 Jun;329(3):1100-9 - PubMed
  23. Gastroenterology. 1984 Dec;87(6):1344-50 - PubMed
  24. Respir Physiol Neurobiol. 2004 Aug 20;142(1):1-11 - PubMed
  25. Diabetes Metab. 2005 Jun;31(3 Pt 1):221-32 - PubMed
  26. Treat Respir Med. 2004;3(3):147-59 - PubMed
  27. J Steroid Biochem Mol Biol. 2005 Jul;96(2):187-200 - PubMed
  28. J Chromatogr A. 2002 Jul 26;964(1-2):137-51 - PubMed
  29. J Pharm Pharmacol. 1972 Feb;24(2):89-102 - PubMed
  30. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1635-9 - PubMed
  31. Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L944-52 - PubMed
  32. Ann N Y Acad Sci. 2006 Jun;1069:236-46 - PubMed
  33. Arch Biochem Biophys. 2001 May 15;389(2):278-87 - PubMed
  34. Clin Rev Allergy Immunol. 2002 Aug;23(1):5-27 - PubMed
  35. Int J Mol Med. 2010 Apr;25(4):625-33 - PubMed
  36. Arch Biochem Biophys. 2006 Dec 1;456(1):1-7 - PubMed
  37. Can Fam Physician. 1999 Jul;45:1723-8 - PubMed
  38. Am J Med Sci. 1993 Aug;306(2):111-6 - PubMed
  39. Psychoneuroendocrinology. 1997;22 Suppl 1:S103-8 - PubMed
  40. Clin Microbiol Rev. 2002 Apr;15(2):194-222 - PubMed
  41. J Neuroimmunol. 2002 Sep;130(1-2):128-39 - PubMed
  42. Clin Rev Allergy Immunol. 2002 Aug;23(1):41-57 - PubMed
  43. Ann N Y Acad Sci. 2007 Sep;1110:630-40 - PubMed
  44. Am J Respir Cell Mol Biol. 2004 Oct;31(4):377-81 - PubMed
  45. Trends Endocrinol Metab. 2002 Sep;13(7):288-94 - PubMed
  46. Pharmacotherapy. 2005 Apr;25(4):555-73 - PubMed
  47. Autoimmun Rev. 2009 Mar;8(5):369-72 - PubMed
  48. Cochrane Database Syst Rev. 2000;(2):CD000304 - PubMed
  49. Ann N Y Acad Sci. 2000;917:860-7 - PubMed
  50. Respir Res. 2006 Apr 07;7:62 - PubMed
  51. Physiol Res. 2003;52(4):397-407 - PubMed
  52. Curr Drug Targets Inflamm Allergy. 2005 Jun;4(3):377-85 - PubMed
  53. J Immunol. 1994 Aug 15;153(4):1544-52 - PubMed
  54. Clin Exp Immunol. 2009 Dec;158(3):308-16 - PubMed
  55. Lab Anim. 2002 Jul;36(3):291-312 - PubMed
  56. Drug Metab Rev. 2006;38(1-2):89-116 - PubMed
  57. Osteoporos Int. 2006;17(5):783-90 - PubMed
  58. Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L717-26 - PubMed
  59. Diabetes Metab Res Rev. 2006 Jan-Feb;22(1):4-10 - PubMed
  60. Proc Soc Exp Biol Med. 1998 Jul;218(3):174-91 - PubMed
  61. Ann N Y Acad Sci. 2009 Sep;1173:781-90 - PubMed
  62. J Chromatogr A. 2001 Nov 23;935(1-2):279-96 - PubMed
  63. J Pharmacol Exp Ther. 2010 Apr;333(1):70-80 - PubMed
  64. Am J Respir Crit Care Med. 2000 Jan;161(1):271-9 - PubMed

Publication Types