Monocytic secretion of interleukin-1 receptor antagonist in normal and osteoporotic women: effects of menopause and estrogen/progesterone therapy.

Interleukin-1 (IL-1), a potent stimulant of bone resorption, has been implicated in the pathogenesis of postmenopausal osteoporosis, because monocyte IL-1 bioactivity increases after the menopause and is decreased by estrogen and progesterone (EP) replacement. As IL-1 bioactivity reflect the production of both IL-1 and the IL-1 inhibitor, IL-1 receptor antagonist (IL-1ra), EP treatment could decrease IL-1 bioactivity by regulating the secretion of either IL-1 or IL-1ra. We now report that EP treatment in vivo decreased the secretion into the medium of cultured monocytes of IL-1ra and IL-1 beta as well as the IL-1 beta/IL-1ra ratio. We also found that in normal women the production of IL-1ra was within premenopausal levels in the first 7 yr after the menopause and increased linearly thereafter. In these women, monocyte IL-1 beta, IL-1 beta/IL-1ra ratio, and IL-1 bioactivity were all increased in the first 7 yr after the menopause and within the premenopausal range thereafter. In osteoporotic women, IL-1 beta, IL-1 beta/IL-1ra ratio, and IL-1 bioactivity increased after the menopause and returned to premenopausal levels after 15 yr from the menopause. In these women monocyte IL-1ra secretion was above the premenopausal range at all times after the menopause, but did not change with the passage of time since menopause. We conclude that hormone replacement decreases the in vitro secretion of both IL-1ra and IL-1 beta. The data also suggest that in normal women a progressive increase in the secretion of IL-1ra contributes to restore a normal IL-1/IL-1ra ratio after the menopause, a phenomenon which, in turn, may play a role in limiting postmenopausal bone loss.