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Effects of Estrogen In Vivo and In Vitro on Spontaneous Interleukin-1 Release by Monocytes From Postmenopausal Women^*

Endocrinology Research Laboratory and Medical Division, Worcester Memorial Hospital Worcester, Massachusetts 01605
The Department of Medicine, University of Massachusetts Medical School Worcester, Massachusetts 01605
The Allergy Division and Department of Medicine, New England Medical Center and Tufts University School of Medicine Boston, Massachusetts 02111

Address requests for reprints to: Dr. John L. Stock, Worcester Memorial Hospital, 119 Belmont Street, Worcester, Massachusetts 01605.

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 17β-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.

^* Presented in part at the 1988 Annual Meeting of the American Federation for Clinical Research. This work was supported in part by a grant frqm the Roger Robinson Research Fund at Worcester Memorial Hospital.

Received June 2, 1988.

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