Role of Interleukin-10 on Nasal Polypogenesis in Patients with Chronic Rhinosinusitis with Nasal Polyps

Background and ObjectivesInterleukin 10 (IL-10) is a potent anti-inflammatory cytokine. The dysregulation of IL-10 is associated with an enhanced immunopathologic response to infection, as well as with an increased risk for developing numerous autoimmune diseases. In this study, we investigated IL-10 expression in chronic rhinosinusitis with nasal polyps (CRSwNP) and assessed the possible role of IL-10 in the pathogenesis of CRSwNP.Materials and MethodsThirty-five patients with CRSwNP, 12 patients with chronic rhinosinusitis without NP (CRSsNP) and 10 control subjects were enrolled in this study. NP tissues and uncinated tissues (UT) were collected for analysis. Dispersed NP cells (DNPCs) were cultured in the presence or absence of IL-25 and IL-10, and a flow cytometric assay was performed to identify the constitutive cell populations of the DNPCs. Murine NP (n = 18) models were used for the in vivo experiments. Real-time PCR, immunohistochemistry, western blotting analysis and ELISA were performed to measure the expression levels of the selected inflammatory cytokines and inflammation-associated molecules.ResultsThe mRNA expression levels of IL-10, IL-5, IL-17A, IL-25 and interferon gamma (IFN-γ) were significantly higher in the NP tissues than in the UT tissues. Strong positive correlations were observed between IL-10 and a variety of inflammatory cytokines (IL-5, IL-17A, IL-25, IFN-γ) and inflammation-associated molecules (B-cell activating factor; BAFF, CD19). Other than the IL-25 to IL-10 ratio, the expression ratios of the other measured inflammatory cytokines to IL-10 were significantly lower in the CRSwNP group than in the CRSsNP or control groups. Administrating IL-25 into the cultured DNPCs significantly increased the production of IL-10, but administrating IL-10 had no effect on the production of IL-25.ConclusionIncreased expression of IL-10, IL-10 related inflammatory cytokine, and IL-10 related B cell activation indicated that IL-10, a potent anti-inflammatory cytokine, has a pivotal role in the pathogenesis of CRSwNPs.

背景与目的
白细胞介素10（Interleukin 10, IL-10）是一种强效抗炎细胞因子。IL-10的表达失调与机体对感染的免疫病理反应增强相关，同时也会增加罹患多种自身免疫性疾病的风险。本研究旨在检测慢性鼻鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps, CRSwNP）患者体内IL-10的表达水平，并探讨IL-10在CRSwNP发病机制中的潜在作用。
材料与方法
本研究共纳入35例慢性鼻鼻窦炎伴鼻息肉患者、12例慢性鼻鼻窦炎不伴鼻息肉（chronic rhinosinusitis without NP, CRSsNP）患者以及10名对照受试者。采集鼻息肉组织与钩突组织（uncinated tissues, UT）用于后续分析。将分散的鼻息肉细胞（dispersed NP cells, DNPCs）分别在添加与不添加IL-25和IL-10的培养基中培养，并通过流式细胞术（flow cytometric assay）鉴定DNPCs的固有细胞群。本研究采用18例小鼠鼻息肉模型开展体内实验。通过实时荧光定量PCR（Real-time PCR）、免疫组织化学（immunohistochemistry）、蛋白质免疫印迹（western blotting）以及酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA），检测选定的炎症细胞因子与炎症相关分子的表达水平。
结果
本研究结果显示，鼻息肉组织中IL-10、IL-5、IL-17A、IL-25及干扰素γ（interferon gamma, IFN-γ）的mRNA表达水平显著高于钩突组织。IL-10与多种炎症细胞因子（IL-5、IL-17A、IL-25、IFN-γ）及炎症相关分子（B细胞活化因子（B-cell activating factor, BAFF）、CD19）呈显著正相关。除IL-25与IL-10的表达比值外，CRSwNP组中其余检测的炎症细胞因子与IL-10的表达比值均显著低于CRSsNP组与对照组。向培养的DNPCs中加入IL-25可显著促进IL-10的产生，而加入IL-10对IL-25的产生无明显影响。
结论
IL-10、IL-10相关炎症细胞因子以及IL-10介导的B细胞活化的表达上调表明，作为强效抗炎细胞因子的IL-10在CRSwNP的发病机制中发挥关键作用。