Neurosurgery Clinic, Jessenius Faculty of Medicine, Martin University Hospital, Comenius University, Kollarova 2, 036 01 Martin, Slovakia.
BioMed (Martin's Biomedical Center), Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin's Biomedical Center (BioMed), Malá Hora, 11161 4D, 036 01 Martin, Slovakia.
Int J Surg. 2017 Jul;43:163-170. doi: 10.1016/j.ijsu.2017.06.024. Epub 2017 Jun 6.
Lumbar degenerative spondylolisthesis (DS) develops as a result of inflammatory and remodeling processes in facet joints (FJs). Several inflammatory cytokines are involved in the osteoarthritic and remodeling changes that occur and in low-back and/or radicular pain, the most prevalent clinical symptom of disease. This study improves knowledge related to the roles that 27 cytokines, chemokines and growth factors play in the pathophysiology of lumbar DS.
Cytokine levels were examined using capture sandwich immunoassay using the Bio-Plex 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) separately in intervertebral discs (IVDs) and FJ bone tissue. The samples were obtained during primary spinal surgery from 9 patients suffering from lower segment lumbar DS. The pain intensity was assessed using a visual analog scale. The controls were tissue samples collected from both lower lumbar segment levels of 6 male subjects during a multiorgan procurement procedure.
The Bio-Plex assay revealed significant differences between the patients and controls in cytokines, chemokines and growth factor profiles: i, The elevated interleukin-6 (IL-6), IL-7, IL-13, tumor necrosis factor α (TNF-α), interferon γ and platelet-derived growth factor levels in lumbar DS samples of subchondral FJ bone. These indicated ongoing inflammation, bone formation and increased fibroblasts activity in the FJ bone. ii, The elevated levels of IL-6, IL-8, TNF-α, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in anulus fibrosus together with increased IL-6, IL-8, TNF-α and eotaxin and decreased IL-1-receptor antagonist in nucleus pulposus confirmed advanced IVD degeneration in the patient samples.
This study identified, for the first time, protective levels of cytokines, chemokines and growth factors in healthy subjects and supported their significant involvement in the pathogenesis of lumbar DS. The control samples and analytical methods used avoided any false changes in the cytokine levels due to secondary factors (e.g., death of donor and limited cytokine stability).
腰椎退行性脊椎滑脱症（DS）是由于小关节（FJ）的炎症和重塑过程而发展的。几种炎症细胞因子参与了发生的骨关节炎和重塑变化，以及下背部和/或神经根疼痛，这是疾病最常见的临床症状。本研究提高了对 27 种细胞因子、趋化因子和生长因子在腰椎 DS 病理生理学中作用的认识。
使用捕获夹心免疫测定法，分别使用 Bio-Plex 200 系统和 Bio-PlexTM 人类细胞因子标准 27- plex，第 I 组（Bio-Rad，加利福尼亚州赫拉克勒斯），在椎间盘（IVD）和 FJ 骨组织中检测细胞因子水平。这些样本是在 9 名患有下段腰椎 DS 的患者的初次脊柱手术中获得的。疼痛强度使用视觉模拟量表进行评估。对照组是在多器官采集过程中从 6 名男性下腰椎段采集的组织样本。
Bio-Plex 分析显示，患者与对照组之间细胞因子、趋化因子和生长因子谱存在显著差异：i，在软骨下 FJ 骨的腰椎 DS 样本中，白细胞介素-6（IL-6）、IL-7、IL-13、肿瘤坏死因子-α（TNF-α）、干扰素γ和血小板衍生生长因子水平升高，表明 FJ 骨中存在持续的炎症、骨形成和成纤维细胞活性增加。ii，在纤维环中，白细胞介素-6、IL-8、TNF-α、粒细胞-巨噬细胞集落刺激因子和单核细胞趋化蛋白-1水平升高，同时在髓核中白细胞介素-6、IL-8、TNF-α和嗜酸性粒细胞趋化因子水平升高，白细胞介素-1 受体拮抗剂水平降低，证实患者样本中 IVD 退变进展。
本研究首次确定了健康受试者中细胞因子、趋化因子和生长因子的保护水平，并支持它们在腰椎 DS 发病机制中的重要作用。使用的对照样本和分析方法避免了由于次要因素（如供体死亡和细胞因子稳定性有限）导致细胞因子水平发生任何虚假变化。
