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/jcem.81.5.8626854
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发表时间：
1996-05
期刊：
影响因子：
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通讯作者：
R. Devlin;H. Bone;G. David Roodman
中科院分区：
文献类型：
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作者：
R. Devlin;H. Bone;G. David Roodman
Gorham-Stout病(GSD)或大量骨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。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，他的下颌骨有大量的吸收，累及上颌、颧骨、右顶区和头盖骨。为了探讨广泛吸收的原因，我们测试了患者血清在治疗早期和骨溶解稳定后对正常人骨髓培养中破骨细胞样多核细胞(MNC)形成的影响。GSD血清(10%，VOL/VOL)能显著增加这些细胞在牙本质片上形成的MNC数量，并刺激这些MNC在牙本质切片上形成吸收陷窝。进一步治疗后收集的GSD血清与正常血清相比，并不增加骨髓培养中MNC的形成数量。早期GSD患者血清IL-6水平升高，是正常范围上限的7倍，进一步治疗后，IL-6水平降至治疗前的1/4。治疗前后GSD患者血清中IL-1β、肿瘤坏死因子-α、转化生长因子-α、甲状旁腺素及甲状旁腺素相关肽水平均未见升高。此外，在正常人骨髓培养中加入IL-6中和抗体，有效地阻断了活性GSD血清诱导的单核细胞形成的增加。提示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患者骨吸收增加中起一定作用。
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 osteoclast-like 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-alpha, 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.