{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:40:08Z","timestamp":1779928808780,"version":"3.53.1"},"reference-count":72,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT2019948"],"award-info":[{"award-number":["GNT2019948"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Septic shock urgently requires new treatments. We reported that low circulating concentrations of the native glucocorticoid carrier, corticosteroid-binding globulin (CBG), predict a 3-fold increase in human septic shock mortality. To explore this, we used our murine model of high-grade polymicrobial sepsis (cecal ligation and puncture [CLP]) to test CBG therapy.<\/jats:p>\n                  <jats:p>We prefitted adult male C57BL\/6 mice (n = 106) with wireless arterial telemetry, then induced high-grade CLP. Mice were randomized with or without intravenous CBG therapy at 6\u2005hours (3.5\u2005mg\/kg) and 30\u2005hours (2.5\u2005mg\/kg). Terminal bloods, collected on humane endpoints or at 96\u2005hours, were assessed for inflammation and organ damage; positron emission tomography was used to assess [124I]I-CBG biodistribution.<\/jats:p>\n                  <jats:p>CLP mice developed septic shock leading to multi-organ failure and 58% mortality. CBG therapy reduced mortality to 17% (a relative decrease of 72%), reduced hypotension duration by 75%, and lowered organ damage markers. CBG transiently suppressed the pro-inflammatory cytokine peak at 12\u2005hours (45%-59%) and markedly augmented anti-inflammatory interleukin-10 and interferon-\u03b21 (2-fold to 96\u2005hours). The decrease in corticosterone alongside this profile suggests an intrinsic anti-inflammatory response. Combined with PET-confirmed [124I]I-CBG targeting to the injury site, these data suggest CBG survival benefits are due to targeted delivery or direct immunomodulation.<\/jats:p>\n                  <jats:p>While host responses involve a complex interplay of neuroendocrine and metabolic factors, our findings demonstrate marked improvements in disease progression and mortality with CBG therapy in murine-modeled septic shock. These results provide a strong impetus for a study of CBG therapy in patients with septic shock.<\/jats:p>","DOI":"10.1210\/endocr\/bqag002","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:40:07Z","timestamp":1767876007000},"source":"Crossref","is-referenced-by-count":2,"title":["Harnessing native corticosteroid-binding globulin to treat life-threatening septic shock"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-3868","authenticated-orcid":false,"given":"Stewart D","family":"Ramsay","sequence":"first","affiliation":[{"name":"Intestinal Sensing Group, University of Adelaide , Adelaide, SA 5005 ,","place":["Australia"]},{"name":"Adelaide Medical School, University of Adelaide , Adelaide, SA 5005 ,","place":["Australia"]},{"name":"Lifelong Health, South Australian Health & Medical Research Institute (SAHMRI) , Adelaide, SA 5000 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SA 5005 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P","family":"Plummer","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, University of Adelaide , Adelaide, SA 5005 ,","place":["Australia"]},{"name":"Intensive Care Unit, Royal Adelaide Hospital , Adelaide, SA 5000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward G","family":"Robins","sequence":"additional","affiliation":[{"name":"Lifelong Health, South Australian Health & Medical Research Institute (SAHMRI) , Adelaide, SA 5000 ,","place":["Australia"]},{"name":"Molecular Imaging and Therapy Research Unit, South Australian Health & Medical Research Institute (SAHMRI) , Adelaide, SA 5000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica H","family":"Lee","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, University of Adelaide , Adelaide, SA 5005 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