Anti-inflammatory and immune regulatory properties of 5-androsten-3β, 17β-diol (HE2100), and synthetic analogue HE3204: Implications for treatment of autoimmune diseases

Dominic Auci, F. Nicoletti, K. Mangano, R. Pieters, S. Nierkens, L. Morgan, H. Offner, J. Frincke, C. Reading

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

5-Androsten-3β, 17β-diol (HE2100), and a synthetic analogue HE3204 are regarded as immune-regulating hormones, because both induce changes in the reporter antigen-popliteal lymph node assay (RA-PLNA). Mice were injected in the footpad with either HE2100 or HE3204 (0.01-3 mg), and a nonsensitizing dose of trinitrophenyl ovalbumin (TNP-OVA) was used as bystander reporter antigen. Seven days later, nodes were removed and numbers of cells (CD3, CD4, CD8, CD19; flow cytometry), TNP-specific IgM, IgG1, and IgG2a antibody-forming cells (AFCs; ELISPOT assay), and cytokines (interleukin-4 [IL-4], interferon-γ [IFN-γ]; ELISA) were measured. HE2100 and HE3204 increased cell numbers in a dose-dependent fashion. T (helper and suppressor) cells and B cells were increased (>5-fold). HE3204 was apparently twice as potent as HE2100. Both increased the B/T ratio (fivefold), increased TNP-specific IgM and IgG1 (∼50-fold), and induced IgG2a AFCs. Both increased IL-4 and IFN-γ secretion (up to threefold). Both displayed anti-inflammatory activity in the murine model of carrageenan-induced pleurisy, as evidenced by reduced neutrophil numbers and exudate volumes. Our observations suggest that both HE2100 and HE3204 are immune-regulating steroid hormones that exhibit anti-inflammatory properties. HE2100 (1 mg/mouse per day) provided significant benefit when given at disease onset in the SJL/J female mouse model of experimental autoimmune encephalomyelitis. These compounds and their analogues are candidates for further testing in autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)730-742
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1051
DOIs
StatePublished - Jan 1 2005

Keywords

  • Autoimmune disease
  • DHEA
  • Immune-regulating hormones
  • Steroids

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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