{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:13:58Z","timestamp":1780316038606,"version":"3.54.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health","award":["K08 GM138825"],"award-info":[{"award-number":["K08 GM138825"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Because of the strong correlation between the blood concentration of circulating resistin and the illness severity of septic patients, resistin has been proposed as a mediator of sepsis pathophysiology. <jats:italic>In vitro<\/jats:italic> data indicate that human resistin directly impairs neutrophil migration and intracellular bacterial killing, although the significance of these findings <jats:italic>in vivo<\/jats:italic> remain unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>The objectives of the present study were: (1) to validate the expression of human resistin in a clinically relevant, murine model of surgical sepsis, (2) to assess how sepsis-induced changes in resistin correlate with markers of infection and organ dysfunction, and (3) to investigate whether the expression of human resistin alters immune function or disease outcomes <jats:italic>in vivo<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>107 male, C57BL\/6 mice transgenic for the human resistin gene and its promoter elements (<jats:italic>Retn<\/jats:italic><jats:sup><jats:italic>+\/\u2212\/\u2212<\/jats:italic><\/jats:sup>, or Retn+) were generated on a <jats:italic>Retn<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> (mouse resistin knockout, or Rko) background. Outcomes were compared between age-matched transgenic and knockout mice. Acute sepsis was defined as the initial 24 h following cecal ligation and puncture (CLP). Physiologic and laboratory parameters correlating to the human Sequential Organ Failure Assessment (SOFA) Score were measured in mice, and innate immune cell number\/function in the blood and peritoneal cavity were assessed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>CLP significantly increased circulating levels of human resistin. The severity of sepsis-induced leukopenia was comparable between Retn+ and Rko mice. Resistin was associated with increased production of neutrophil reactive oxygen species, a decrease in circulating neutrophils at 6 h and an increase in peritoneal Ly6C<jats:sup>hi<\/jats:sup> monocytes at 6 h and 24 h post-sepsis. However, intraperitoneal bacterial growth, organ dysfunction and mouse survival did not differ with resistin production in septic mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Significance<\/jats:title>\n<jats:p><jats:italic>Ex vivo<\/jats:italic> resistin-induced impairment of neutrophil function do not appear to translate to increased sepsis severity or poorer outcomes <jats:italic>in vivo<\/jats:italic> following CLP.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0265241","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T17:40:52Z","timestamp":1647279652000},"page":"e0265241","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Resistin production does not affect outcomes in a mouse model of acute surgical sepsis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-001X","authenticated-orcid":true,"given":"Anthony S.","family":"Bonavia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zissis C.","family":"Chroneos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Ruiz-Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"issue":"6","key":"pone.0265241.ref001","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1097\/01.CCM.0000266536.14736.03","article-title":"Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock","volume":"35","author":"J Sunden-Cullberg","year":"2007","journal-title":"Crit Care Med"},{"key":"pone.0265241.ref002","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1471-2482-10-26","article-title":"Sepsis induced changes of adipokines and cytokines\u2014septic patients compared to morbidly obese patients.","volume":"10","author":"A Hillenbrand","year":"2010","journal-title":"BMC Surg"},{"key":"pone.0265241.ref003","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cyto.2019.03.002","article-title":"Circulating eNampt and resistin as a proinflammatory duet predicting independently mortality in critically ill patients with sepsis: A prospective observational study","volume":"119","author":"I Karampela","year":"2019","journal-title":"Cytokine"},{"issue":"10","key":"pone.0265241.ref004","doi-asserted-by":"crossref","first-page":"e110678","DOI":"10.1371\/journal.pone.0110678","article-title":"Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis\/septic shock in the emergency department","volume":"9","author":"SP Macdonald","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"pone.0265241.ref005","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jcrc.2012.04.007","article-title":"Serial changes in adiponectin and resistin in critically ill patients with sepsis: associations with sepsis phase, severity, and circulating cytokine levels","volume":"27","author":"DA Vassiliadi","year":"2012","journal-title":"J Crit Care"},{"issue":"10","key":"pone.0265241.ref006","doi-asserted-by":"crossref","first-page":"e13333","DOI":"10.1111\/eci.13333","article-title":"The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial","volume":"50","author":"A Bonaventura","year":"2020","journal-title":"Eur J Clin 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