{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:57:39Z","timestamp":1792684659562,"version":"4.5.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"crossref","award":["E-26\/210.4001\/2019"],"award-info":[{"award-number":["E-26\/210.4001\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes.<\/jats:p>","DOI":"10.1371\/journal.pone.0262785","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T19:26:56Z","timestamp":1642534016000},"page":"e0262785","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cytokines and inflammatory mediators: Markers involved in interstitial damage to the pancreas in two dengue fever cases associated with acute pancreatitis"],"prefix":"10.1371","volume":"17","author":[{"given":"Felipe de Andrade Vieira","family":"Alves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucca de Lima S.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia Gede\u00e3o","family":"Salom\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David William","family":"Provance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto","family":"Basilio-de-Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Bas\u00edlio-de-Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Junqueira","family":"Moragas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Jos\u00e9","family":"de Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronaldo","family":"Mohana-Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-7788","authenticated-orcid":true,"given":"K\u00edssila","family":"Rabelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marciano Viana","family":"Paes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"pone.0262785.ref001","first-page":"1","article-title":"Global epidemiology of dengue outbreaks in 1990\u20132015: A systematic review and meta-analysis","volume":"7","author":"C Guo","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0262785.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41426-018-0168-0","article-title":"Dengue virus and the host innate immune response","volume":"7","author":"N Uno","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"pone.0262785.ref003","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.glohj.2019.06.002","article-title":"Dengue epidemiology.","volume":"3","author":"Q Jing","year":"2019","journal-title":"Glob Heal J"},{"key":"pone.0262785.ref004","first-page":"1","article-title":"Dengue with Hemorrhagic Manifestations and Acute Pancreatitis: Case Report and Review.","volume":"11","author":"R Correa","year":"2019","journal-title":"Cureus"},{"key":"pone.0262785.ref005","first-page":"71","article-title":"Atypical manifestations of dengue fever\u2014Where do we stand today?","volume":"8","author":"S Sudhish Nimmagadda","year":"2014","journal-title":"J Clin Diagnostic Res"},{"key":"pone.0262785.ref006","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1590\/0037-8682-0145-2016","article-title":"Acute pancreatitis complicating dengue hemorrhagic fever.","volume":"49","author":"KJ Kumar","year":"2016","journal-title":"Rev Soc Bras Med Trop"},{"key":"pone.0262785.ref007","doi-asserted-by":"crossref","first-page":"153","DOI":"10.14740\/gr858w","article-title":"Review of Infectious Etiology of Acute Pancreatitis.","volume":"10","author":"P Rawla","year":"2017","journal-title":"Gastroenterol Res."},{"key":"pone.0262785.ref008","doi-asserted-by":"crossref","first-page":"676","DOI":"10.18203\/2349-3291.ijcp20180581","article-title":"Acute Pancreatitis: a late complication of dengue fever.","volume":"5","author":"K A. 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