A synthetic androstene derivative and a natural androstene metabolite inhibit relapsing-remitting EAE

Halina Offner, Alex Zamora, Heather Drought, Agata Matejuk, Dominick L. Auci, Elizabeth E. Morgan, Arthur Vandenbark, Christopher L. Reading

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Experimental allergic encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the central nervous system (CNS), shares many pathological and clinical similarities with multiple sclerosis (MS), and thus represents an attractive animal model for this disease. The goal of this study was to evaluate the suppressive effects of fluasterone (HE2500), a synthetic androstene derivative, and androstenetriol (HE2200), a natural androstene hormone on EAE. SJL mice were immunized with proteolipid protein (PLP) 139-151 peptide/CFA to induce EAE. Starting on day -7, animals were given daily injections (s.c.) of derivatives (3.0 mg) in vehicle, or vehicle alone for 33 days. Both HE2500 and HE2200 significantly delayed the onset, reduced the peak clinical score and cumulative disease index of EAE, and prevented or significantly attenuated relapses. Lower doses or other routes of administration were less effective. Moreover, T cells from treated mice had significantly reduced PLP 139-151-specific T cell proliferation responses and reduced numbers of TNF-α- and IFN-γ-producing cells in the CNS. Daily treatment of B10.PL mice with HE2500, starting on day 0, completely prevented the development of disease in these animals. Finally, SJL mice treated with HE2500 at EAE onset showed significantly reduced mean clinical scores. Thus, these compounds, which have been reported to have a few androgenic or estrogenic side effects, appear to have a potent inhibitory activity in EAE. These observations suggest that HE2500 and/or HE2200 limit the production of autoimmune Th1 associated cytokines, and ultimately may be beneficial for patients with MS or other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)128-139
Number of pages12
JournalJournal of Neuroimmunology
Volume130
Issue number1-2
DOIs
StatePublished - Sep 2002
Externally publishedYes

Fingerprint

Androstenes
Autoimmune Experimental Encephalomyelitis
Multiple Sclerosis
Central Nervous System
T-Lymphocytes
Animal Disease Models
Animal Diseases
Demyelinating Diseases
Autoimmune Diseases
5-androstene-16-fluoro-17-one
Estrogens
Cell Proliferation
Hormones
Cytokines
Recurrence
Peptides
Injections

Keywords

  • Androstene
  • Cytokines
  • DHEA
  • EAE
  • MS

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

A synthetic androstene derivative and a natural androstene metabolite inhibit relapsing-remitting EAE. / Offner, Halina; Zamora, Alex; Drought, Heather; Matejuk, Agata; Auci, Dominick L.; Morgan, Elizabeth E.; Vandenbark, Arthur; Reading, Christopher L.

In: Journal of Neuroimmunology, Vol. 130, No. 1-2, 09.2002, p. 128-139.

Research output: Contribution to journalArticle

Offner, Halina ; Zamora, Alex ; Drought, Heather ; Matejuk, Agata ; Auci, Dominick L. ; Morgan, Elizabeth E. ; Vandenbark, Arthur ; Reading, Christopher L. / A synthetic androstene derivative and a natural androstene metabolite inhibit relapsing-remitting EAE. In: Journal of Neuroimmunology. 2002 ; Vol. 130, No. 1-2. pp. 128-139.
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