TY - JOUR
T1 - Anti-inflammatory and immune regulatory properties of 5-androsten-3β, 17β-diol (HE2100), and synthetic analogue HE3204
T2 - Implications for treatment of autoimmune diseases
AU - Auci, Dominic
AU - Nicoletti, F.
AU - Mangano, K.
AU - Pieters, R.
AU - Nierkens, S.
AU - Morgan, L.
AU - Offner, H.
AU - Frincke, J.
AU - Reading, C.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Autoimmune disease
KW - DHEA
KW - Immune-regulating hormones
KW - Steroids
UR - http://www.scopus.com/inward/record.url?scp=25444502312&partnerID=8YFLogxK
U2 - 10.1196/annals.1361.117
DO - 10.1196/annals.1361.117
M3 - Article
C2 - 16127013
AN - SCOPUS:25444502312
SN - 0077-8923
VL - 1051
SP - 730
EP - 742
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -