Nakchbandi I A, Mitnick M A, Masiukiewicz U S, Sun B H, Insogna K L
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
Endocrinology. 2001 Sep;142(9):3850-6. doi: 10.1210/endo.142.9.8368.
IL-6 and IL-11 are two cytokines that increase osteoclast formation and augment bone resorption. PTH stimulates the production of both cytokines by human osteoblast-like cells. Circulating levels of IL-6 are elevated in patients with states of PTH excess and correlate strongly to markers of bone resorption. In contrast, serum levels of IL-11 were significantly reduced in patients with primary hyperparathyroidism compared with values in euparathyroid controls. Further, after successful parathyroid adenomectomy, circulating levels of IL-6 fell, whereas IL-11 levels increased. Five-day infusions of human PTH-(1--84) in rodents resulted in a significant decline in mean circulating levels of IL-11, whereas IL-6 levels significantly increased. Pretreatment of cells and mice with neutralizing serum to IL-6 enhanced PTH-induced IL-11 production compared with the effect of pretreatment with nonimmune sera. These data indicate that IL-6 negatively regulates IL-11 production in vivo and in vitro. Analysis of steady state mRNA levels in SaOS-2 cells indicated that this effect is posttranscriptional. As both IL-6 and IL-11 stimulate osteoclast formation, down-regulation of IL-11 by IL-6 may help modulate the resorptive response to PTH.
白细胞介素-6（IL-6）和白细胞介素-11（IL-11）是两种可增加破骨细胞形成并增强骨吸收的细胞因子。甲状旁腺激素（PTH）刺激人成骨样细胞产生这两种细胞因子。PTH分泌过多状态的患者中，IL-6的循环水平升高，且与骨吸收标志物密切相关。相比之下，原发性甲状旁腺功能亢进患者的血清IL-11水平与甲状旁腺功能正常的对照者相比显著降低。此外，成功进行甲状旁腺腺瘤切除术后，IL-6的循环水平下降，而IL-11水平升高。在啮齿动物中连续5天输注人PTH-（1-84）导致IL-11的平均循环水平显著下降，而IL-6水平显著升高。与用非免疫血清预处理的效果相比，用抗IL-6中和血清预处理细胞和小鼠可增强PTH诱导的IL-11产生。这些数据表明，IL-6在体内和体外对IL-11的产生具有负调节作用。对SaOS-2细胞中稳态mRNA水平的分析表明，这种作用是转录后水平的。由于IL-6和IL-11均刺激破骨细胞形成，IL-6对IL-11的下调可能有助于调节对PTH的吸收反应。
