{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:34:14Z","timestamp":1790786054542,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T00:00:00Z","timestamp":1420675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Royal Adelaide Hospital Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Summary<\/jats:title>\n \n Objective<\/jats:title>\n \n Corticosteroid\u2010binding globulin (\n CBG<\/jats:styled-content>\n ) is cleaved by neutrophil elastase converting the high\u2010affinity (ha\n CBG<\/jats:styled-content>\n ) conformation of\n CBG<\/jats:styled-content>\n to a low\u2010affinity (la\n CBG<\/jats:styled-content>\n ) conformation with a ninefold reduced cortisol\u2010binding affinity. These\n in vitro<\/jats:italic>\n data suggest that cortisol release by\n CBG<\/jats:styled-content>\n cleavage results in the targeted delivery of cortisol to areas of inflammation. Our objective was to determine whether\n CBG<\/jats:styled-content>\n cleavage alters circulating levels of ha\n CBG<\/jats:styled-content>\n and la\n CBG<\/jats:styled-content>\n in vivo<\/jats:italic>\n in proportion to sepsis severity.\n <\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Prospective, observational cohort study in an adult tertiary level Intensive Care Unit in Adelaide, Australia.<\/jats:p>\n <\/jats:sec>\n \n Patients<\/jats:title>\n Thirty\u2010three patients with sepsis or septic shock grouped by illness severity [sepsis, septic shock survivors, septic shock nonsurvivors and other shock].<\/jats:p>\n <\/jats:sec>\n \n Measurements<\/jats:title>\n \n Plasma levels of ha\n CBG<\/jats:styled-content>\n and la\n CBG<\/jats:styled-content>\n were assessed using a recently developed in\u2010house assay in patients. Plasma total and free cortisol levels were also measured.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Plasma total\n CBG<\/jats:styled-content>\n and ha\n CBG<\/jats:styled-content>\n levels fell significantly, in proportion to disease severity (\n P\u00a0<\/jats:italic>\n <\u00a00\u00b70001 for both). There was a nonsignificant increase in free and total cortisol as illness severity worsened (\n P\u00a0<\/jats:italic>\n =\u00a00\u00b719 and\n P\u00a0<\/jats:italic>\n =\u00a00\u00b739, respectively). Illness severity was better correlated with ha\n CBG<\/jats:styled-content>\n levels than either free or total cortisol levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Increasing illness severity in sepsis and septic shock is associated with markedly reduced circulating ha\n CBG<\/jats:styled-content>\n concentrations\n in vivo<\/jats:italic>\n . We propose that low levels of ha\n CBG<\/jats:styled-content>\n in chronic inflammation may limit the availability of cortisol to inflammatory sites, perpetuating the inflammatory process.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cen.12680","type":"journal-article","created":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T02:31:50Z","timestamp":1416450710000},"page":"801-807","source":"Crossref","is-referenced-by-count":51,"title":["Depletion of high\u2010affinity corticosteroid\u2010binding globulin corresponds to illness severity in sepsis and septic shock; clinical implications"],"prefix":"10.1111","volume":"82","author":[{"given":"M.A.","family":"Nenke","sequence":"first","affiliation":[{"name":"Endocrine and Metabolic Unit Royal Adelaide Hospital Adelaide SA Australia"},{"name":"School of Medicine University of Adelaide Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Rankin","sequence":"additional","affiliation":[{"name":"Chemical Pathology Directorate SA Pathology Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.J.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Intensive Care Unit Royal Adelaide Hospital Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.E.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Laboratory Hanson Institute and Sansom Institute University of South Australia Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.R.","family":"Diener","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Laboratory Hanson Institute and Sansom Institute University of South Australia Adelaide SA Australia"},{"name":"Robinson Research Institute and School of Paediatrics and Reproductive Health University of Adelaide Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D.","family":"Hayball","sequence":"additional","affiliation":[{"name":"School of Medicine University of Adelaide Adelaide SA Australia"},{"name":"Experimental Therapeutics Laboratory Hanson Institute and Sansom Institute University of South Australia Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Steroid and Immunobiochemistry Laboratory Canterbury Health Laboratories Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.J.","family":"Torpy","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Unit Royal Adelaide Hospital Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.11.3758"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2012.11.016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.15.5153"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/336257a0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-71-1-34"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.05.012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705014200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052759"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.171082"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4280"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.12.015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0942"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.08.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.7.862"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071366"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0265"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318239b809"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199206000-00025"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2014.01.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.03.044"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214969"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69005-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1203"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2006.06.031"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1988.tb48873.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1987.tb01145.x"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12680","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12680","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T13:04:10Z","timestamp":1695560650000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,8]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/cen.12680"],"URL":"https:\/\/doi.org\/10.1111\/cen.12680","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725242904.793501888","asserted-by":"object"}]},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,8]]}}}