Interleukin-6: A potential mediator of the massive osteolysis in patients with Gorham-Stout disease
Interleukin-6: A potential mediator of the massive osteolysis in patients with Gorham-Stout disease
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DOI：
10.1210/jc.81.5.1893
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发表时间：
1996-05-01
影响因子：
5.8
通讯作者：
Roodman, GD
中科院分区：
文献类型：
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作者：
Devlin, RD;Bone, HG;Roodman, GD
Gorham-Stout 病 (GSD) 或称大规模骨质溶解，是一种极其罕见的溶骨性疾病，涉及广泛的局部侵袭性骨吸收。其病因和病理生理学尚不清楚，破骨细胞在 GSD 中的作用也不清楚。我们研究了一名患有 GSD 的患者，他的下颌骨发生了严重的吸收，并延伸到了上颌骨、颧骨、右顶叶区域和颅骨。为了调查广泛吸收的原因，我们测试了在治疗过程早期和骨溶解稳定后采集的患者血清对正常人骨髓培养物中破骨细胞样多核细胞（MNC）形成的影响。与正常血清相比，GSD 血清（10%，vol/vol）显着增加了这些培养物中形成的 MNC 数量，并刺激了这些 MNC 在牙本质切片上形成吸收凹坑。进一步治疗后收集的 GSD 血清与正常血清相比，并未增加骨髓培养物中形成的 MNC 数量。早期GSD血清中检测到白细胞介素6（IL-6）水平升高，为正常范围上限的7倍，进一步治疗后，IL-6水平降至治疗前值的四分之一。治疗前GSD血清中IL-1β、肿瘤坏死因子-ct、转化生长因子-α、PTH和PTH相关肽的水平未升高。此外，向正常人骨髓培养物中添加IL-6中和抗体可有效阻止活性GSD血清诱导的MNC形成增加。这些数据表明GSD患者的骨吸收是由于破骨细胞活性增强所致，IL-6可能在GSD骨吸收增加中发挥作用。
Gorham-Stout disease (GSD) or massive osteolysis, is an extremely rare osteolytic condition that involves extensive locally aggressive resorption of bone. The etiology and pathophysiology are unknown, and the role of the osteoclast in GSD is unclear. We studied a patient with GSD who had massive resorption of his mandible, which extended to his maxilla, zygoma, right parietal region, and cranium. To investigate the cause of the extensive resorption, we tested the effects of the patient's serum, sampled early in the course of treatment and later after the osteolysis was stabilized, on the formation of osteoclastlike multinucleated cells (MNC) in cultures of normal human marrow. GSD serum (10%, vol/vol) markedly increased the number of MNC formed in these cultures compared to that in normal serum as well as stimulated the formation of resorption pits by these MNC on dentine slices. GSD serum, collected after further therapy, did not enhance the number of MNC formed in marrow cultures compared to that in normal serum. Elevated levels of interleukin-6 (IL-6) were detected in the earlier GSD serum that were 7 times the upper Limit of the normal range, and after further treatment, IL-6 levels fell to one quarter the pretreatment value. The levels of IL-1 beta, tumor necrosis factor-ct, transforming growth factor-alpha, PTH, and PTH-related peptide in pretreatment GSD serum were not increased. Moreover, the addition of neutralizing antibodies to IL-6 to the normal human bone marrow cultures effectively blocked the increase in MNC formation induced by active GSD serum. These data suggest that bone resorption in GSD patients is due to enhanced osteoclast activity, and that IL-6 may play a role in the increased bone resorption in GSD.