Previous studies have suggested that the inflammatory response contributes to the onset of intervertebral disc degeneration (IVDD). Interleukin (IL)-38, a newly discovered cytokine of the IL-1 family, has been demonstrated to play an anti-inflammatory role in autoimmune diseases, such as Crohn’s disease, rheumatoid arthritis and psoriasis. However, whether IL-38 participates in the pathogenesis of IVDD remains unknown. In this study, human disc tissues from IVDD patients and rat disc tissues from an IVDD model were collected to measure the expression of IL-38 in the IVDD groups and the control groups by western blot and immunohistochemical staining. To further determine the role of IL-38 in IVDD, human nucleus pulposus cells (HNPCs) were stimulated with TNF-α to generate an in vitro model of inflammation to mimic the local inflammatory environment of the lumbar disc. The inflammatory response and HNPC degeneration markers were measured after stimulation with TNF-α and IL-38. IL-38 was upregulated in both the human and rat degenerated disc tissues compared with the control tissues. In vitro, IL-38 significantly decreased the TNF-α-induced expression of IL-1β, IL-6, COX-2, MMP-13 and ADAMTS-5 in the HNPCs, and IL-38 also alleviated the TNF-α-induced reductions in type II collagen and aggrecan. Moreover, IL-38 inhibited the activation of the NF-κB signaling pathway in the HNPC-based model of inflammation by reducing the expression level of the NF-κB P-P65 protein. In conclusion, IL-38 could alleviate the inflammatory response and HNPC degeneration in vitro via the inhibition of the NF-κB signaling pathway. These results suggest that IL-38 may be a new strategy for the treatment of IVDD.

先前的研究表明，炎症反应有助于椎间盘退变（IVDD）的发作。白介素（IL）-38是一种新发现的IL-1家族的细胞因子，已被证明在自身免疫疾病（如克罗恩病，类风湿性关节炎和牛皮癣）中具有抗炎作用。但是，IL-38是否参与IVDD的发病机制仍不清楚。在这项研究中，收集了来自IVDD患者的人椎间盘组织和来自IVDD模型的大鼠椎间盘组织，以通过Western印迹和免疫组化染色测量IVDD组和对照组中IL-38的表达。为了进一步确定IL-38在IVDD中的作用，用TNF-α刺激人髓核细胞（HNPC）生成体外炎症模型，以模拟腰椎间盘的局部炎症环境。在用TNF-α和IL-38刺激后，测量炎症反应和HNPC变性标记。与对照组织相比，人和大鼠变性椎间盘组织中的IL-38均上调。在体外，IL-38显着降低HNPC中TNF-α诱导的IL-1β，IL-6，COX-2，MMP-13和ADAMTS-5的表达，IL-38也减轻TNF-α-导致II型胶原蛋白和聚集蛋白聚糖减少。此外，IL-38通过降低NF-κBP-P65蛋白的表达水平，抑制了基于HNPC的炎症模型中NF-κB信号通路的激活。结论，IL-38可通过抑制NF-κB信号通路减轻炎症反应和HNPC变性。这些结果表明，IL-38可能是治疗IVDD的新策略。