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aHollis-Eden Pharmaceuticals, San Diego, California, USA bDepartment of Biomedical Sciences, School of Medicine, University of Catania, Catania, Italy cInstitute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands dDepartment of Neurology, Oregon Health and Science University, Portland, Oregon, USA
Address for correspondence: Dominick L. Auci, 4435 Eastgate Mall, Suite 400, San Diego, CA 92121. Voice: 858-320-2582; fax: 858-558-6470. Dauci{at}holliseden.com
5-Androsten-3ß, 17ß-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-
 [IFN-]; 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- 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.
Key Words: steroids • DHEA • autoimmune disease • immune-regulating hormones
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