{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:23:52Z","timestamp":1787217832746,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The liver is essential for bacterial elimination, preventing intestinal bacteria from entering the systemic circulation, and for producing inflammatory cytokines. Glucocorticoids have been reported to exert heterogeneous effects on bacterial clearance in sepsis. Using a porcine model of gram\u2010negative abdominal sepsis, we investigated how portal venous administration of budesonide, a glucocorticoid with extensive hepatic first\u2010pass metabolism, affects hepatic bacterial and endotoxin elimination as well as the systemic inflammatory response, in comparison with systemic administration and no treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The Portal Steroid\u2010Sepsis (Sep\u2010Port,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) and Systemic Steroid\u2010Sepsis (Sep\u2010Syst,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) groups were administered budesonide in the portal vein or systemically, followed by an\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>E. coli<\/jats:italic>\n                      <\/jats:styled-content>\n                      infusion for 3\u2009h in the portal vein. The Septic Controls (Sep\u2010Ctrl,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) received saline instead of budesonide. Non\u2010septic Controls (NSep\u2010Port,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) were treated only with portal budesonide. Portal, arterial, and hepatic venous bacterial counts were analyzed hourly during the bacterial infusion. The levels of endotoxin and inflammatory cytokines were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was no difference in hepatic\/portal venous bacterial count ratios. However, the arterial and hepatic venous bacterial counts were higher in the Sep\u2010Syst compared to Sep\u2010Port group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01, respectively), while microbiological findings were similar in the Sep\u2010Port and Sep\u2010Ctrl groups. Hepatic endotoxin elimination did not differ between the groups. IL\u201010 levels were higher in the Sep\u2010Port compared to the Sep\u2010Syst group at 1\u2009h (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and IL\u20106 levels were lower in the Sep\u2010Port compared to the Sep\u2010Ctrl after the bacterial infusion (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this experimental sepsis model, hepatic bacterial elimination was unaffected by portal or systemic budesonide, whereas systemic administration was associated with increased systemic bacterial levels. Endotoxin clearance was unaffected by budesonide. Portal budesonide elicited a more pronounced anti\u2010inflammatory response compared to systemic administration. These findings suggest that hepatic exposure to budesonide may modulate the inflammatory response while limiting adverse effects on systemic bacterial clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Editorial Comment<\/jats:title>\n                    <jats:p>Glucocorticoids are widely used in sepsis management, yet their effects on bacterial clearance is incompletely understood. In this porcine model of gram\u2010negative abdominal sepsis, portal venous delivery of budesonide (which has ~90% hepatic first\u2010pass metabolism) preserved bacterial elimination and enhanced the early anti\u2010inflammatory response, without the increase in systemic bacterial levels seen with systemic administration. These results demonstrate that route of delivery as a potentially important determinant of the risk\u2010benefit balance of glucocorticoid therapy in sepsis, and support further investigation of hepatic\u2010targeting strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aas.70312","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:02:11Z","timestamp":1784858531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Regional Hepatic Immunosuppression With Budesonide on Bacterial Elimination in Porcine Abdominal Sepsis"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1101-1683","authenticated-orcid":false,"given":"Katja","family":"Hanslin","sequence":"first","affiliation":[{"name":"Anesthesiology and Intensive Care, Department of Surgical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5407-6612","authenticated-orcid":false,"given":"Paul","family":"Skorup","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida","family":"Wilske","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-0402","authenticated-orcid":false,"given":"Anders","family":"Larsson","sequence":"additional","affiliation":[{"name":"Section of Clinical Chemistry, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3058-0769","authenticated-orcid":false,"given":"Eva","family":"Tano","sequence":"additional","affiliation":[{"name":"Section of Clinical Bacteriology, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sj\u00f6lin","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-4129","authenticated-orcid":false,"given":"Miklos","family":"Lipcsey","sequence":"additional","affiliation":[{"name":"Anesthesiology and Intensive Care, Department of Surgical Sciences Uppsala University  Uppsala Sweden"},{"name":"Hedenstierna Laboratory, Department of Surgical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.45"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.SLA.0000055274.56407.71"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2204019"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.5.9702108"},{"issue":"6","key":"e_1_2_13_6_1","first-page":"669","article-title":"Role of Cytokines as a Double\u2010Edged Sword in Sepsis","volume":"27","author":"Chaudhry H.","year":"2013","journal-title":"In Vivo"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2013.tb00510.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.110.1.27"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.889129"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-198103000-00004"},{"issue":"286","key":"e_1_2_13_11_1","first-page":"281","article-title":"Review of the Significance of Pulmonary Intravascular Macrophages With Respect to Animal Species and Age","volume":"57","author":"Winkler G. 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