Effects of estrogen in vivo and in vitro on spontaneous interleukin-1 release by monocytes from postmenopausal women.
Estrogen (E) inhibits bone resorption, but the mechanism of this effect is unknown. Interleukin-1 (IL-1) stimulates bone resorption in vitro and may be produced in bone by mononuclear phagocytes. Recently, the spontaneous release of IL-1 from peripheral monocytes was found to reflect bone formation in a subset of patients with idiopathic osteoporosis. We suspected that the action of E on bone is mediated indirectly by its effect on monocyte IL-1 activity. Eleven normal postmenopausal women taking no medications were given conjugated E (0.625 mg daily) for 3-9 weeks. Supernatants from cultured peripheral monocytes were analyzed for IL-1 production by stimulation of a cloned murine helper T-cell line. IL-1 release was expressed as a percentage of maximum release corrected for monocyte number. IL-1 release before E treatment was 11.0 +/- 0.2% (+/- SE), it was 7.8 +/- 1.6% after E treatment (P = NS). IL-1 release fell in each of the three women with the highest initial values (46% to 5%, 25% to 17%, and 18% to 12%). IL-1 release did not correlate with serum osteocalcin or fasting urinary calcium either before or after E treatment. Addition of 10(-7)-10(-10) mol/L 17 beta-estradiol to cultured monocytes obtained before E treatment caused an increase in IL-1 release that did not follow a dose-response relationship. Treatment of postmenopausal women with E did not affect spontaneous IL-1 release by peripheral monocytes in vitro. The addition of E in vitro did not produce consistent changes in IL-1 release by these cells. This does not exclude the possibility that E may affect monocyte IL-1 release in subsets of women with high spontaneous monocyte IL-1 release with or without osteoporosis.
Endocrinology Research Laboratory, Worcester Memorial Hospital, Massachusetts 01605.
J L
JL
Stock
J A
JA
Coderre
B
B
McDonald
L J
LJ
Rosenwasser
D000328:Adult; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism
D004967:Estrogens; D007375:Interleukin-1