之前的证据表明，幽门螺杆菌引起的炎症是胃癌发生的第一步。然而，有关驱动这一过程的免疫因素的调查显示出了不一致性。我们旨在全面总结与幽门螺杆菌感染和胃癌有关的所有研究过的细胞因子，以及将其与全球胃癌风险联系起来。我们进行了系统回顾和串联荟萃分析，识别所有已发表的研究中报告血清细胞因子水平在H. pylori感染个案与非感染对照组以及胃癌个案与非胃癌对照组之间的差异，进行亚分析以确定全球地区间的细胞因子诱导差异及其与胃癌发生率的相关性。仅系统性IL-6（标准化平均差异[SMD]：0.95，95％CI [0.45;1.45]）和TNF-α（SMD：0.88，95％CI [0.46;1.29]）的水平在感染H. pylori时显著增加。亚分析显示，H. pylori感染后IL-6水平在东亚，中东和东南亚人群中增加，但在北美，欧洲，俄罗斯和非洲地区没有增加。IL-6，IL-7，IL-10，IL-12和TNF-α的血清水平在胃癌中显著升高。探索H. pylori感染后血清细胞因子变化与胃癌患病风险的地区差异的关系表明，IL-6血清水平的SMD与相对胃癌发生率显著相关（r = 0.81，p = 0.00014）。本研究显示，H. pylori感染和胃癌与IL-6和TNF-α水平升高相关。特别是，IL-6表现出区域特定的增加，与胃癌发生率相关，成为该疾病的主要原因之一。版权所有© 2023 Yu，Xiang，Peppelenbosch和Fuhler。

Previous evidence indicated that Helicobacter pylori-induced inflammation is the first step towards gastric carcinogenesis. However, investigations of the immunological factors driving this process have shown inconsistencies. We aimed to present a thorough summary of all researched cytokines in relation to H. pylori infection and GC and relate these to global GC risk.We performed a systematic review and tandem meta-analysis identifying all published studies reporting on serum cytokine levels in H. pylori-infected cases vs. non-infected controls and gastric cancer cases vs. non-gastric cancer controls, with sub-analyses performed to identify global regional differences in cytokine induction and their correlation with GC incidence.Only levels of systemic IL-6 (standardized mean difference [SMD]:0.95, 95%CI [0.45;1.45]) and TNF-α (SMD:0.88, 95%CI [0.46; 1.29]) were significantly increased upon H. pylori infection. Sub-analysis showed that of IL-6 levels were increased upon H. pylori infection in East Asian, Middle Eastern and Southeast Asian cohorts, but not in North America, Europe, Russia and Africa. Serum levels of IL-6, IL-7, IL-10, IL-12, and TNF-α were significantly raised in GC. Exploration of the relationship between serum cytokines changes upon H. pylori infection and regional differences in risk of GC development indicated that the SMD of IL-6 serum levels presents a significant correlation with the relative incidence of GC (r=0.81, p=0.00014).This study shows that H. pylori infection and GC are associated with increased IL-6 and TNF-α levels. Particularly, IL-6 shows region-specific increases that correlate with GC incidence, making it a key contender for the cause of this disease.Copyright © 2023 Yu, Xiang, Peppelenbosch and Fuhler.