{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:56:11Z","timestamp":1792007771042,"version":"4.4.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the\n                      <jats:italic>IL1RN<\/jats:italic>\n                      gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97,\n                      <jats:italic>P<\/jats:italic>\n                      =0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82,\n                      <jats:italic>P<\/jats:italic>\n                      =2.93\u00d710\n                      <jats:sup>-8<\/jats:sup>\n                      ) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96,\n                      <jats:italic>P<\/jats:italic>\n                      =0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1240754","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T14:54:18Z","timestamp":1694703258000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Therapeutic role of interleukin-1 receptor antagonist in pancreatic diseases: mendelian randomization 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