本系统综述和荟萃分析旨在评估复发性口疮性口炎(RAS)中各种T辅助(Th)细胞分泌的细胞因子的表达水平。在PubMed中搜索了比较RAS患者和健康对照之间血清或唾液细胞因子水平的病例对照研究。EMBASE,WebofScience,和谷歌学者在2023年9月30日之前。Th1产生的细胞因子(白细胞介素[IL]-1,IL-2,IL-8,IL-12,肿瘤坏死因子α[TNF-α],干扰素γ[IFN-γ]),Th2(IL-4,IL-5,IL-6,IL-10,IL-13),研究Th17(IL-17A)细胞。计算具有95%置信区间(CI)的标准平均差(SMD)以检测差异。共纳入20项研究,包括1070例RAS患者和536例健康对照。RAS患者唾液IL-2水平显著升高(SMD=4.15,95CI0.83-7.48),IL-5(SMD=0.53,95CI0.05-1.00),IL-6(SMD=0.48,95CI0.12-0.84),IL-12(SMD=0.94,95CI0.18-1.71),与健康对照组相比,TNF-α(SMD=1.31,95CI0.44-2.18)。血清IL-6水平(SMD=0.48,95CI0.30-0.66),TNF-α(SMD=0.70,95CI0.22-1.17),和IFN-γ(SMD=0.72,95CI0.17-1.28)明显升高,而RAS患者的血清IL-10水平(SMD=-2.25,95CI-3.99至-0.52)降低。诊断为主要RAS的患者血清IL-8水平显着升高(SMD=0.39,95CI0.07-0.71),并且血清IL-6水平(SMD=0.51,95CI-0.02至1.04)的趋势高于次要RAS。总之,Th1/Th2相关细胞因子,特别是IL-2、IL-6和TNF-α,参与RAS发生发展的发病机制,是RAS的潜在治疗靶点。
This systematic review and meta-analysis aimed to evaluate the expression levels of various T helper (Th) cell-secreted cytokines in recurrent aphthous stomatitis (RAS). Case-control studies comparing the serum or salivary levels of cytokines between RAS patients and healthy controls were searched in PubMed, EMBASE, Web of Science, and Google Scholar prior to September 30, 2023. Cytokines produced by Th1 (interleukin [IL]-1, IL-2, IL-8, IL-12, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17A) cells were investigated. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated to detect the difference. A total of 20 studies comprising 1070 RAS patients and 536 healthy controls were included. RAS patients had significantly higher salivary levels of IL-2 (SMD = 4.15, 95%CI 0.83-7.48), IL-5 (SMD = 0.53, 95%CI 0.05-1.00), IL-6 (SMD = 0.48, 95%CI 0.12-0.84), IL-12 (SMD = 0.94, 95%CI 0.18-1.71), and TNF-α (SMD = 1.31, 95%CI 0.44-2.18) compared to healthy controls. Serum levels of IL-6 (SMD = 0.48, 95%CI 0.30-0.66), TNF-α (SMD = 0.70, 95%CI 0.22-1.17), and IFN-γ (SMD = 0.72, 95%CI 0.17-1.28) were significantly increased, while serum IL-10 levels (SMD = -2.25, 95%CI -3.99 to -0.52) were reduced in RAS patients. Patients diagnosed with major RAS had markedly elevated serum IL-8 levels (SMD = 0.39, 95%CI 0.07-0.71) and a trend toward higher serum IL-6 levels (SMD = 0.51, 95%CI -0.02 to 1.04) than those with minor RAS. In conclusion, Th1/Th2-related cytokines, especially IL-2, IL-6, and TNF-α, are involved in the pathogenesis of RAS development and progression and are potential therapeutic targets for RAS.