{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:02:04Z","timestamp":1789653724459,"version":"4.0.0"},"reference-count":50,"publisher":"Life Science Alliance, LLC","issue":"8","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 AI080581"],"award-info":[{"award-number":["R01 AI080581"]}]},{"name":"Tulane University Dean Funds"}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Reports indicate that accumulated macrophages in the pancreas are responsible for promoting the pathogenesis of chronic pancreatitis (CP). Recently, macrophage-secreted cytokines have been implicated in promoting pancreatic acinar-to-ductal metaplasia (ADM). This study aims to establish the role of accumulated macrophage-activated NLRP3-IL-18-eosinophil mechanistic pathway in promoting several characteristics of pancreatic malignancy in CP. We report that in a murine model of pancreatic cancer (PC), accumulated macrophages are the source of NLRP3-regulated IL-18, which promotes eosinophilic inflammation-mediated accumulation to periductal mucin and collagen, including the formation of ADM, pancreatic intraepithelial neoplasia (PanINs), and intraductal papillary mucinous neoplasm. Most importantly, we show improved malignant characteristics with reduced levels of oncogenes in an anti\u2013IL-18 neutralized and IL-18 gene deficient murine model of CP. Last, human biopsies validated that NLRP3-IL-18\u2013induced eosinophils accumulate near the ducts, showing PanINs formation in PC. Taken together, we present the evidence on the role of IL-18\u2013induced eosinophilia in the development of PC phenotype like ADM, PanINs, and ductal cell differentiation in inflammation-induced CP.<\/jats:p>","DOI":"10.26508\/lsa.202000979","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T12:40:57Z","timestamp":1624884057000},"page":"e202000979","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Macrophages-induced IL-18\u2013mediated eosinophilia promotes characteristics of pancreatic malignancy"],"prefix":"10.26508","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-3341","authenticated-orcid":true,"given":"Hemanth Kumar","family":"Kandikattu","sequence":"first","affiliation":[{"name":"Department of Medicine, Tulane Eosinophilic Disorders Centre, Section of Pulmonary Diseases, School of Medicine, Tulane University, New Orleans, LA, 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