{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T20:31:11Z","timestamp":1775421071609,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cytokine Storm Syndrome (CSS) is a severe immune dysregulation characterized by excessive cytokine release and multi-organ injury. Existing murine models inadequately replicate human CSS. This study aimed to establish a D-galactosamine (D-GalN)-induced miniature pig model to investigate multi-organ pathological changes and inflammatory dynamics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-four male minipigs were divided into control and D-GalN groups (n=12 each). The experimental group received 1.5 g\/kg D-GalN intravenously. At 0 h, 12 h, 24 h, and 36 h post-induction, tissues from the liver, lungs, intestines, heart, spleen, and kidneys were collected for hematoxylin-eosin (H&amp;amp;E) staining and IL-6 immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Histopathology revealed progressive, time-dependent multi-organ injury. The liver, lungs, and intestines showed the earliest and most severe damage, including hepatocellular necrosis, alveolar congestion, and intestinal epithelial destruction. IL-6 expression increased over time, first peaking in the liver and later spreading to the lungs, intestines, and other organs. At 36 h, IL-6 was diffusely expressed in hepatic and pulmonary tissues, indicating an escalating systemic inflammatory response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This minipig CSS model replicates human-like disease progression and identifies the liver as a likely initiator of systemic inflammation. The observed \u201cliver initiation\u2013lung and intestine diffusion\u201d pattern provides new insights into CSS pathogenesis. The temporal expression of IL-6 suggests a critical therapeutic window prior to 24 h post-onset for anti-inflammatory interventions, including artificial liver support and IL-6 blockade.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1618665","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T04:14:29Z","timestamp":1753244069000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Multi-organ pathology in a small porcine model of cytokine storm syndrome characteristics"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiaqian","family":"Jin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linxiao","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanhao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sainan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengfei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3760\/cma.j.issn.1674-2397.2024.01.002","article-title":"National Clinical Research Center for Infectious Diseases, National Key Laboratory for Infectious Disease Diagnosis and Treatment. 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