{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:29:30Z","timestamp":1792290570859,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["413635475"],"award-info":[{"award-number":["413635475"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BE\u201063951"],"award-info":[{"award-number":["BE\u201063951"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Obstruction of the pancreatic duct by impacted gallstones at the level of the papilla vateri causes acute pancreatitis. How non\u2010obstructing stones such as microlithiasis or sludge cause pancreatitis has not been studied. We aimed to understand the pathomechanism of microlithiasis\u2010induced acute pancreatitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In human papillary biopsies from patients with microlithiasis\u2010induced acute pancreatitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04), alcohol\u2010induced acute pancreatitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05), and control subjects without pancreatobiliary disease (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04), the inflammatory infiltrate was quantified. Bone marrow\u2013derived macrophages generated from C57BL\/6 mice were treated in vitro with cholesterol monohydrate and calcium bilirubinate crystals, and NLRP3 inflammasome\u2010mediated macrophage activation was quantified. Microlithiasis formation in the gallbladder was induced in mice through lithogenic high fat diet and devazepide. Acute pancreatitis was induced by supramaximal caerulein stimulation. Microlithiasis ejection from the gallbladder was achieved through low\u2010dose caerulein i.p. Injections. Pancreatitis severity was compared between caerulein\u2010induced pancreatitis and caerulein\u2010induced pancreatitis after repetitive microlithiasis ejection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significantly higher infiltration of CD45\u2010positive leukocytes and increased NLRP3 expression were observed in papillary biopsies from patients with microlithiasis\u2010induced acute pancreatitis compared with patients with alcohol\u2010induced acute pancreatitis and control subjects. In line with this, significantly higher IL\u20101\u00df secretion and caspase\u20101 activation were observed in vitro in bone marrow\u2010derived macrophages stimulated with cholesterol monohydrate and calcium billirubinate crystals. In vivo microlithiasis formation was achieved in all mice with high fat diet and devazepide. Compared to caerulein\u2010induced pancreatitis, in caerulein\u00a0+\u00a0microlithiasis pancreatitis, higher LDH, GPT and ALP levels in serum were observed, but without an impact on pancreatitis severity. However, mice papilla mimicked the phenotype of microlithiasis\u2010induced acute pancreatitis in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We propose a novel mechanism in which biliary microlithiasis induces a local inflammatory reaction at the papilla (acute papillitis) via NLRP3 inflammasome activation driven by bone marrow\u2010derived macrophages, without causing pancreatic outflow obstruction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ueg2.70198","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:54:22Z","timestamp":1773492862000},"source":"Crossref","is-referenced-by-count":2,"title":["NLRP3 Inflammasome Activation\u2010Induced Acute Papillitis as a Trigger of Acute Pancreatitis \u2010 A Novel Mechanism of Microlithiasis\u2010Induced Acute Pancreatitis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-334X","authenticated-orcid":false,"given":"Simon","family":"Sirtl","sequence":"first","affiliation":[{"name":"Department of Medicine II University Hospital LMU  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-2324","authenticated-orcid":false,"given":"Mahmood","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Medicine II University Hospital LMU  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prince","family":"Allawadhi","sequence":"additional","affiliation":[{"name":"Department of Medicine II University Hospital LMU  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Metzler","sequence":"additional","affiliation":[{"name":"Comparative Experimental Pathology (CEP) Technical University of Munich  Munich 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