Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats
Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats
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DOI：
10.1002/art.34456
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发表时间：
2012-08-01
影响因子：
--
通讯作者：
Kurosaka, Masahiro
中科院分区：
文献类型：
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作者：
Takada, Toru;Nishida, Kotaro;Kurosaka, Masahiro
目的研究肿瘤坏死因子α（TNF α）、白细胞介素6（IL-6）、白细胞介素8（IL-8）、前列腺素E2（PGE 2）等炎症因子在椎间盘突出症中的表达。在不同类型的免疫细胞中，巨噬细胞经常出现在突出的椎间盘组织中。我们进行了这项研究，以澄清椎间盘（IVD）和巨噬细胞在TNF α，IL-6，IL-8和PGE 2的产生方面的相互作用。方法我们建立了两种动物模型，以评估IVD与巨噬细胞在TNF α、IL-6、IL-8和PGE 2产生和疼痛相关行为方面的相互作用。我们还将IVD和巨噬细胞共培养以评估TNF α在IL-6、IL-8和PGE 2产生中的作用。结果IVD自体移植物诱导TNFa、IL-6、IL-8和环加氧酶2（考克斯-2）信使RNA（mRNA）上调;自体移植物植入后不久就出现巨噬细胞浸润。在TNF α、IL-6、IL-8和考克斯-2 mRNA上调后，注意到同侧爪的机械阈值显著降低。只有IVD和巨噬细胞共培养导致IL-8和PGE 2上调。TNF α上调在IL-6和IL-8上调之前最大化。TNF α中和减弱IL-6和PGE 2的产生，但不减弱IL-8的产生。TNF α和IL-8的中和显著增加了IVD自体移植物和脊神经结扎模型中的缩爪机械阈值。结论IVD-巨噬细胞相互作用在坐骨神经痛和TNF α、IL-6、IL-8和PGE 2的产生中起主要作用。在IVD巨噬细胞相互作用期间，TNF α是IL-6和PGE 2产生所需的，但不是IL-8产生所需的。TNFa和IL-8的中和可以是椎间盘突出疾病的有价值的疗法。
Objective The expression of proinflammatory factors such as tumor necrosis factor a (TNFa), interleukin-6 (IL-6), IL-8, and prostaglandin E2 (PGE2) is significantly correlated with the symptoms of herniated disc disease. Among the different types of immune cells, macrophages are frequently noted in the herniated disc tissue. We undertook this study to clarify the interaction of the intervertebral disc (IVD) and macrophages with regard to the production of TNFa, IL-6, IL-8, and PGE2. Methods We developed 2 animal models to assess the interactions of IVDs with macrophages in terms of TNFa, IL-6, IL-8, and PGE2 production and pain-related behavior. We also cocultured IVDs and macrophages to assess the role of TNFa in IL-6, IL-8, and PGE2 production. Results IVD autografts induced TNFa, IL-6, IL-8, and cyclooxygenase 2 (COX-2) messenger RNA (mRNA) up-regulation; macrophage infiltration was seen shortly after the autograft was implanted. A significant decrease was noted in the mechanical threshold of the ipsilateral paw following the up-regulation of TNFa, IL-6, IL-8, and COX-2 mRNA. Only IVD and macrophage cocultures resulted in IL-8 and PGE2 up-regulation. TNFa up-regulation was maximized before that of IL-6 and IL-8. TNFa neutralization attenuated production of IL-6 and PGE2, but not that of IL-8. Neutralization of TNFa and IL-8 significantly increased the paw withdrawal mechanical threshold in the IVD autograft and spinal nerve ligation model. Conclusion IVDmacrophage interaction plays a major role in sciatica and in the production of TNFa, IL-6, IL-8, and PGE2. TNFa is required for IL-6 and PGE2 production, but not for IL-8 production, during IVDmacrophage interaction. Neutralization of TNFa and IL-8 can be a valuable therapy for herniated disc disease.