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

Abstract

5-Androsten-3beta, 17beta-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-gamma [IFN-gamma]; 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 ( approximately 50-fold), and induced IgG2a AFCs. Both increased IL-4 and IFN-gamma 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.

• Authors: D Auci, F Nicoletti, K Mangano, R Pieters, S Nierkens, L Morgan, H Offner, J Frincke, C Reading
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1051 Pg. 730-42 (Jun 2005) ISSN: 0077-8923 [Print] United States
• PMID: 16127013 (Publication Type: Journal Article)

Chemical References

• Androstenols
• Anti-Inflammatory Agents
• HE3204
• Androstenediol

Topics

• Amino Acid Sequence
• Androstenediol (analogs & derivatives, pharmacology, therapeutic use)
• Androstenols (pharmacology, therapeutic use)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Autoimmune Diseases (drug therapy)
• Encephalomyelitis, Autoimmune, Experimental (drug therapy)
• Female
• Male
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• Pleurisy (drug therapy)
• Shock, Septic (drug therapy)