{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:18:22Z","timestamp":1792419502101,"version":"4.5.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"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":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Procalcitonin (PCT) is expressed in nonthryoidal tissues of humans during severe infections. Serum PCT levels are measured to diagnose and guide therapy, and there is some evidence that PCT may also contribute to the pathogenesis of sepsis. We tested whether disruption of the gene encoding PCT in mice affected the course of sepsis. Mice with exons 2\u20135 of the gene encoding calcitonin\/calcitonin gene\u2013related polypeptide \u03b1 (Calca) knocked out and congenic C57BL\/6J control mice were challenged with aerosolized Streptococcus pneumoniae or Pseudomonas aeruginosa, or injected intraperitoneally with S. pneumoniae. There were no significant differences in the survival of knockout and control mice in the two pneumonia models, and no significant differences in weight loss, splenic bacterial counts, or blood leukocyte levels in the peritoneal sepsis model. To verify disruption of the Calca gene in knockout mice, the absence of calcitonin in the serum of knockout mice and its presence and inducibility in control mice were confirmed. To evaluate PCT expression in nonthyroidal tissues of control mice, transcripts were measured in multiple organs. PCT transcripts were not significantly expressed in liver or spleen of control mice challenged with aerosolized P. aeruginosa or intraperitoneal endotoxin, and were expressed in lung only at low levels, even though serum IL-6 rose 3,548-fold. We conclude that mice are not an ideal loss-of-function model to test the role of PCT in the pathogenesis of sepsis because of low nonendocrine PCT expression during infection and inflammation. Nonetheless, our studies demonstrate that nonendocrine PCT expression is not necessary for adverse outcomes from sepsis.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0489oc","type":"journal-article","created":{"date-parts":[[2013,3,23]],"date-time":"2013-03-23T01:02:38Z","timestamp":1364000558000},"page":"151-155","source":"Crossref","is-referenced-by-count":8,"title":["Deletion of the Gene Encoding Calcitonin and Calcitonin Gene\u2013Related Peptide \u03b1 Does Not Affect the Outcome of Severe Infection in Mice"],"prefix":"10.1093","volume":"49","author":[{"given":"Michael J.","family":"Tuvim","sequence":"first","affiliation":[{"name":"Departments of Pulmonary Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia G.","family":"Clement","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Su-Chen Huang","sequence":"additional","affiliation":[{"name":"Endocrine Neoplasia and Hormonal Disorders, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert J.","family":"Cote","sequence":"additional","affiliation":[{"name":"Endocrine Neoplasia and Hormonal Disorders, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiudong","family":"Lei","sequence":"additional","affiliation":[{"name":"Biostatistics, The University of Texas M. 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Anderson Cancer Center, Houston, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard J.","family":"Deftos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of California San Diego and Veterans Administration Medical Center, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Gagel","sequence":"additional","affiliation":[{"name":"Endocrine Neoplasia and Hormonal Disorders, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton F.","family":"Dickey","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,1]]},"reference":[{"key":"2026021904244035500_bib1","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1097\/CCM.0b013e3181726819","article-title":"Calcitonin peptides\u2014the mediators in sepsis or just another fairy tale?","volume":"36","author":"Christ-Crain","year":"2008","journal-title":"Crit Care Med"},{"key":"2026021904244035500_bib2","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1172\/JCI200214218","article-title":"Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene","volume":"110","author":"Hoff","year":"2002","journal-title":"J Clin Invest"},{"key":"2026021904244035500_bib3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/1741-7015-9-107","article-title":"Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future","volume":"9","author":"Schuetz","year":"2011","journal-title":"BMC Med"},{"key":"2026021904244035500_bib4","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1097\/CCM.0b013e31821e8791","article-title":"Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial","volume":"39","author":"Jensen","year":"2011","journal-title":"Crit Care Med"},{"key":"2026021904244035500_bib5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.diagmicrobio.2012.05.002","article-title":"Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis","volume":"73","author":"Riedel","year":"2012","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2026021904244035500_bib6","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1097\/00003246-199806000-00015","article-title":"Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis","volume":"26","author":"Nylen","year":"1998","journal-title":"Crit Care Med"},{"key":"2026021904244035500_bib7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1089\/109629601317202678","article-title":"Late immunoneutralization of procalcitonin arrests the progression of lethal porcine sepsis","volume":"2","author":"Martinez","year":"2001","journal-title":"Surg Infect (Larchmt)"},{"key":"2026021904244035500_bib8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1042\/CS20100007","article-title":"Immunoneutralization of the aminoprocalcitonin peptide of procalcitonin protects rats from lethal endotoxaemia: neuroendocrine and systemic studies","volume":"119","author":"Tavares","year":"2010","journal-title":"Clin Sci (Lond)"},{"key":"2026021904244035500_bib9","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1097\/00003246-200210000-00021","article-title":"Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs","volume":"30","author":"Wagner","year":"2002","journal-title":"Crit Care Med"},{"key":"2026021904244035500_bib10","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1164\/rccm.200607-1038OC","article-title":"Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice","volume":"177","author":"Clement","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021904244035500_bib11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1165\/rcmb.2008-0260OC","article-title":"Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi","volume":"42","author":"Evans","year":"2010","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026021904244035500_bib12","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/0026-0495(71)90037-0","article-title":"Immunoassay for human calcitonin. 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