{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:46:38Z","timestamp":1771533998110,"version":"3.50.1"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"12","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>Severe sepsis and septic shock are an important cause of mortality and morbidity. These illnesses can be triggered by the bacterial endotoxin LPS (lipopolysaccharide) and pro-inflammatory cytokines, particularly TNF-\u03b1 (tumour necrosis factor-\u03b1) and IL (interleukin)-1\u03b2. Severity and mortality of sepsis have also been associated with high concentrations of N-PCT (aminoprocalcitonin), a 57-amino-acid neuroendocrine peptide derived from ProCT (procalcitonin). Previous studies in a lethal model of porcine polymicrobial sepsis have revealed that immunoneutralization with IgG that is reactive to porcine N-PCT significantly improves short-term survival. To explore further the pathophysiological role of N-PCT in sepsis, we developed an antibody raised against a highly conserved amino acid sequence of human N-PCT [N-PCT-(44\u201357)]. This sequence differs by only one amino acid from rat N-PCT. First, we demonstrated the specificity of this antibody in a well-proven model of anorexia induced in rats by central administration of human N-PCT-(1\u201357). Next we explored further the therapeutic potential of anti-N-PCT-(44\u201357) in a rat model of lethal endotoxaemia and determined how this immunoneutralization affected LPS-induced lethality and cytokine production. We show that this specific antibody inhibited the LPS-induced early release of TNF-\u03b1 and IL-1\u03b2 and increased survival, even if treatment began after the cytokine response had occurred. In addition, anti-N-PCT-(44\u201357) may increase long-term survival in LPS-treated rats by up-regulating the late production of counter-regulatory anti-inflammatory mediators such as ACTH (adrenocorticotropic hormone) and IL-10. In conclusion, these results support N-PCT as a pro-inflammatory factor in both the early and the late stages of lethal endotoxaemia, and suggest anti-N-PCT as a candidate for septic shock therapy.<\/jats:p>","DOI":"10.1042\/cs20100007","type":"journal-article","created":{"date-parts":[[2010,6,24]],"date-time":"2010-06-24T11:27:01Z","timestamp":1277378821000},"page":"519-534","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Immunoneutralization of the aminoprocalcitonin peptide of procalcitonin protects rats from lethal endotoxaemia: neuroendocrine and systemic studies"],"prefix":"10.1042","volume":"119","author":[{"given":"Eva","family":"Tavares","sequence":"first","affiliation":[{"name":"Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville 41014, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco\u00a0J.","family":"Mi\u00f1ano","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville 41014, Spain"},{"name":"Department of Pharmacology, Pediatrics and Radiology, Faculty of Medicine, University of Seville, Seville 41011, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2010,9,1]]},"reference":[{"key":"2021113010133810400_B1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu. 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