{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:04:39Z","timestamp":1789362279738,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005366","name":"Universitetet i Oslo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"publisher"}]}],"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>Ischemia\u2013reperfusion injury remains a major challenge in liver transplantation and plays a major role in pathophysiology leading to graft failure. Machine perfusion (MP) is a promising approach to restitute marginal donor livers. However, the impact of MP on innate immunity remains insufficiently defined. We hypothesized that MP activates the innate inflammatory response. Thus, we investigated whether the ischemic injury and perfusate composition [plasma-rich perfusate (PRP) versus plasma-poor perfusate (PPP)] modulate the inflammatory response, identified by complement activation and cytokine release.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty porcine livers were subjected to\n                      <jats:italic>ex situ<\/jats:italic>\n                      MP. The first 24 porcine livers were subject to induced biliary ischemic injury (BileINJ,\n                      <jats:italic>n<\/jats:italic>\n                      = 8), global ischemic injury (GlobalINJ,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08), or no induced ischemic injury (CTRL,\n                      <jats:italic>n<\/jats:italic>\n                      = 8) using PRP during MP. The subsequent six porcine livers were subjected to the same\n                      <jats:italic>ex situ<\/jats:italic>\n                      MP protocol using PPP (\n                      <jats:italic>n<\/jats:italic>\n                      = 6) with no induced ischemic injury. MP was conducted in three phases: 1\u00a0h hypothermic, 1\u00a0h controlled rewarming, and 4\u00a0h normothermic perfusion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Except for interleukin-1\u03b2 (IL-1\u03b2) in bile tissue in the BileINJ group and tumor necrosis factor (TNF) in plasma in the GlobalINJ group, all mediators assessed whether in perfusate, liver, or bile tissue did not differ significantly between ischemic injury groups and CTRL. Data were therefore combined into a common PRP group for further comparisons. In PRP perfusate, MP induced robust complement activation (sC5b-9: median fold change (FC) 4 [2\u20136 interquartile range]) and cytokine release (IL-1\u03b2: FC 88 [51\u2013165], IL-6: FC 1,549 [587\u20133,053], IL-8: FC 389 [120\u20131,259], IL-10: FC 404 [222\u2013656], all\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). This pattern persisted in PPP group perfusate, liver, and bile tissue, though the concentrations were significantly lower compared to PRP (sC5b-9, IL-10, IL-6, IL-1\u03b2, and IL-8, all\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Liver MP reliably induced innate immune-driven inflammation regardless of prior ischemic injury. The magnitude of the inflammatory response was substantially lower in the PPP group compared to the PRP group. Future therapeutic trials targeting innate immunity during\n                      <jats:italic>ex situ<\/jats:italic>\n                      MP are warranted to improve the preservation of liver grafts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1874888","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:37:56Z","timestamp":1789360676000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune activation during liver machine perfusion is shaped by perfusate composition and is independent of the ischemic injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Ida H.","family":"F\u00e6rden","sequence":"first","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]},{"name":"Division of Emergencies and Critical Care, Oslo University Hospital Rikshospitalet","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte","family":"Bliks\u00f8en","sequence":"additional","affiliation":[{"name":"Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Schjalm","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Pettersen","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital","place":["Bod\u00f8, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav M. 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B.","family":"Liav\u00e5g","sequence":"additional","affiliation":[{"name":"Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed M.","family":"Majeed","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Hagness","sequence":"additional","affiliation":[{"name":"Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom E.","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital 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