{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T17:02:54Z","timestamp":1775322174386,"version":"3.50.1"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70\u2212\/\u2212 and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70\u2212\/\u2212 and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70\u2212\/\u2212 mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70\u2212\/\u2212 mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70\u2212\/\u2212 mice had increased systemic levels of TNF-\u03b1, IL-6, IL-10, and IL-1\u03b2 compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.1003652","type":"journal-article","created":{"date-parts":[[2011,2,5]],"date-time":"2011-02-05T03:23:14Z","timestamp":1296876194000},"page":"3718-3725","source":"Crossref","is-referenced-by-count":47,"title":["The Role of Heat Shock Protein 70 in Mediating Age-Dependent Mortality in Sepsis"],"prefix":"10.1093","volume":"186","author":[{"given":"Kevin W","family":"McConnell","sequence":"first","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy C","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew T","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nai-Yuan Nicholas","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Denver School of Medicine, University of Colorado , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alton B","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy G","family":"Buchman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Emory University School of Medicine , Atlanta, GA 30322"},{"name":"Emory Center for Critical Care, Emory University Woodruff Health Sciences Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clayton R","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern School of Medicine , Dallas, TX 75390"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig M","family":"Coopersmith","sequence":"additional","affiliation":[{"name":"Department of Surgery, Emory University School of Medicine , Atlanta, GA 30322"},{"name":"Emory Center for Critical Care, Emory University Woodruff Health Sciences Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,3,15]]},"reference":[{"key":"2025032411145361200_r1","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1021\/jm100054f","article-title":"Heat shock protein 70 (hsp70) as an emerging drug target","volume":"53","author":"Evans","year":"2010","journal-title":"J. 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