The effect of 17β-estradiol on production of cytokines in cultures of peripheral blood

Estrogen’s action on bone may be mediated by cytokines produced by monocytes. We have reported a decreased ratio of interleukin-1β (IL-1β) to interleukin-1 receptor antagonist (IL-1ra) produced by whole blood cultures in vivo in women taking hormone replacement therapy (HRT). Also, one study has shown an effect of estradiol on tumor necrosis factor-α (TNF-α) secretion by separated monocytes in vitro. The aim of this study was to evaluate the effect of estrogen in vitro on the secretion of cytokines using whole blood cultures. Subjects consisted of 12 healthy postmenopausal women, ages 57–69 years, 4–20 years since menopause. Cytokines IL-1β, interleukin-1α (IL-1α), IL-1ra, interleukin-6 (IL-6), TNF-α, and granulocyte macrophage-colony stimulating factor (GM-CSF) were measured in unstimulated and in stimulated (500 ng/mL lipopolysaccharide [LPS]) whole blood cultures treated with 17β-estradiol (E2) at concentrations of 10−12–10−6 mol/L. We found significant decreases in the spontaneous secretion of IL-6, TNF-α, IL-1ra, IL-1β, and ratio of IL-1β/IL-1ra compared with control, at physiological concentrations of E2. The action of E2 was blocked by the use of the antiestrogen ICI 182780 in coculture. A decrease in cytokine secretion was not observed when the inactive form of estrogen, 17α-estradiol, was used in place of 17β-estradiol. GM-CSF and IL-1α were not detectable in unstimulated cultures. Cytokine levels measured in stimulated cultures were not attenuated by treatment with E2. We conclude that E2 inhibits the spontaneous secretion of cytokines measured in whole blood cultures at physiological concentrations, and that the powerful stimulatory effect of LPS prevents any significant inhibition by E2 in stimulated cultures.