Pacifici R, Vannice J L, Rifas L, Kimble R B
Division of Bone and Mineral Disease, Washington University School of Medicine, St. Louis, Missouri 63110.
J Clin Endocrinol Metab. 1993 Nov;77(5):1135-41. doi: 10.1210/jcem.77.5.8077304.
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.
白细胞介素-1（IL-1）是一种强大的骨吸收刺激因子，与绝经后骨质疏松症的发病机制有关，因为绝经后单核细胞IL-1生物活性增加，而雌激素和孕激素（EP）替代治疗可使其降低。由于IL-1生物活性反映了IL-1及其抑制剂白细胞介素-1受体拮抗剂（IL-1ra）的产生，EP治疗可能通过调节IL-1或IL-1ra的分泌来降低IL-1生物活性。我们现在报告，体内EP治疗可减少培养单核细胞培养基中IL-1ra、IL-1β的分泌以及IL-1β/IL-1ra比值。我们还发现，正常女性在绝经后的前7年中，IL-1ra的产生处于绝经前水平，此后呈线性增加。在这些女性中，绝经后的前7年单核细胞IL-1β、IL-1β/IL-1ra比值和IL-1生物活性均增加，此后处于绝经前范围内。在骨质疏松症女性中，绝经后IL-1β、IL-1β/IL-1ra比值和IL-1生物活性增加，绝经15年后恢复到绝经前水平。在这些女性中，绝经后单核细胞IL-1ra分泌始终高于绝经前范围，但不随绝经时间的推移而变化。我们得出结论，激素替代可减少IL-1ra和IL-1β的体外分泌。数据还表明，在正常女性中，IL-1ra分泌的逐渐增加有助于在绝经后恢复正常的IL-1/IL-1ra比值，这一现象反过来可能在限制绝经后骨质流失中起作用。
