AUTHOR=Yu Bingting , Xiang Luochengling , Peppelenbosch Maikel P. , Fuhler Gwenny M. 

TITLE=Overlapping cytokines in H. pylori infection and gastric cancer: A tandem meta-analysis

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1125658

DOI=10.3389/fimmu.2023.1125658

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Previous evidence indicated that <italic>Helicobacter pylori</italic>-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 <italic>H. pylori</italic> infection and GC and relate these to global GC risk.</p></sec><sec><title>Methods</title><p>We performed a systematic review and tandem meta-analysis identifying all published studies reporting on serum cytokine levels in <italic>H. pylori</italic>-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.</p></sec><sec><title>Results</title><p>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 <italic>H. pylori</italic> infection. Sub-analysis showed that of IL-6 levels were increased upon <italic>H. pylori</italic> 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 <italic>H. pylori</italic> 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 (<italic>r</italic>=0.81, <italic>p</italic>=0.00014).</p></sec><sec><title>Conclusion</title><p>This study shows that <italic>H. pylori</italic> 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.</p></sec>