Human nucleus pulposis can respond to a pro-inflammatory stimulus
Human nucleus pulposis can respond to a pro-inflammatory stimulus
复制标题
DOI：
10.1097/01.brs.0000103341.45133.f3
复制
发表时间：
2003-12-15
期刊：
影响因子：
3
通讯作者：
Fitzpatrick, JM
中科院分区：
文献类型：
--
作者：
Burke, JG;Watson, RWG;Fitzpatrick, JM
研究设计.从接受脊柱侧凸、腰椎神经根病和椎间盘源性疼痛手术的患者中获得的椎间盘组织在基础和脂多糖刺激条件下培养，并分析培养基中一系列促炎介质的产生。本研究旨在证实人类椎间盘能够对促炎刺激做出反应，并确定参与任何反应的主要介质。已经显示退化的人类椎间盘组织自发地分泌许多促炎介质。这些分子在症状性椎间盘退变的病理生理学中的重要性越来越被认识到。人类髓核在受到IL-1 β刺激后，其合成的白细胞介素（IL）-6、前列腺素E-2（PGE（2））和一氧化氮的量增加。小鼠髓核对脂多糖刺激的反应是合成大量IL-1 β、IL-6、IL-10和粒细胞-巨噬细胞集落刺激因子。脂多糖是肿瘤坏死因子-α（TNF-α）的强效诱导剂，其被认为在坐骨神经痛的病理生理学中起重要作用。迄今为止，尚未显示人髓核响应于促炎刺激而分泌TNF-α。从脊柱侧凸、腰椎神经根病和椎间盘源性疼痛患者手术中获得的人类椎间盘组织在基础和脂多糖刺激条件下培养，随后分析培养基中的一系列促炎介质。所有标本均未产生任何TNF-α、IL-1 β、粒细胞-巨噬细胞集落刺激因子或白三烯B4。大量标本产生可测量数量的IL-6、IL-8、PGE（2）、MCP-1、碱性成纤维细胞生长因子和转化生长因子β 1。脂多糖显著增加对照组和退变椎间盘组织中IL-6、IL-8和PGE（2）的产生。退变椎间盘标本对脂多糖刺激的反应比脊柱侧凸椎间盘标本更强烈。我们的结论是，脊柱侧凸和退变的人类髓核都可以通过分泌增加的IL-6、IL-8和PGE（2）而不是TNF-α来对外源性促炎刺激做出反应，并且退变的椎间盘组织比脊柱侧凸的椎间盘组织对促炎刺激更敏感。
Study Design. Disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium analyzed for production of a range of pro-inflammatory mediators.Objectives. This study was conducted to confirm that the human intervertebral disc is capable of responding to a pro-inflammatory stimulus and to identify the principal mediators involved in any response.Summary of Background Data. Degenerate human disc tissue has been shown to spontaneously secrete a number of pro-inflammatory mediators. The importance of these molecules in the pathophysiology of symptomatic disc degeneration is increasingly recognized. Human nucleus pulposus has been shown to synthesize increased amounts of interleukin (IL)-6, prostaglandin E-2 (PGE(2)), and nitric oxide in response to stimulation with IL-1beta. Murine nucleus pulposus synthesizes increased amounts of IL-1beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor in response to lipopolysaccharide stimulation. Lipopolysaccharide is a potent inducer of tumor necrosis factor-alpha (TNF-alpha), which is thought to play an important role in the pathophysiology of sciatica. To date, human nucleus pulposus has not been shown to secrete TNF-alpha in response to a pro-inflammatory stimulus.Methods. Human disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium subsequently analyzed for a range of pro-inflammatory mediators.Results. None of the specimens produced any TNF-alpha, IL-1beta, granulocyte-macrophage colony-stimulating factor, or leukotriene B4. Measurable quantities of IL-6, IL-8, PGE(2), MCP-1, basic fibroblast growth factor, and transforming growth factor-beta1 were produced by a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and PGE(2) production in both control and degenerate disc tissue. Degenerate disc specimens responded more vigorously to lipopolysaccharide stimulation than scoliotic specimens.Conclusions. We conclude that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE(2) but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.