| Immunoneutralization of the aminoprocalcitonin peptide of procalcitonin protects rats from lethal endotoxaemia: neuroendocrine and systemic studies. | |
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MedLine Citation:
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PMID: 20569200 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-α (tumour necrosis factor-α) and IL (interleukin)-1β. 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-(44-57)]. 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-(1-57). Next we explored further the therapeutic potential of anti-N-PCT-(44-57) 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-α and IL-1β and increased survival, even if treatment began after the cytokine response had occurred. In addition, anti-N-PCT-(44-57) 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. |
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Authors:
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Eva Tavares; Francisco J Miñano |
Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 119 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-20 Completed Date: 2011-01-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 519-34 Citation Subset: IM |
Affiliation:
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Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcitonin / genetics, immunology*, metabolism, pharmacology Cytokines / biosynthesis Disease Models, Animal Eating / drug effects Endotoxemia / immunology, metabolism, prevention & control* Gene Expression Hypothalamus / metabolism Immunotherapy / methods* Inflammation Mediators / blood Lipopolysaccharides Male Peptide Fragments / immunology Protein Precursors / genetics, immunology*, metabolism, pharmacology Rats Rats, Wistar Survival Analysis |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Inflammation Mediators; 0/Lipopolysaccharides; 0/Peptide Fragments; 0/Protein Precursors; 56645-65-9/procalcitonin; 9007-12-9/Calcitonin |
| Comments/Corrections | |
Comment In:
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Clin Sci (Lond). 2010 Dec;119(12):515-7
[PMID:
20649514
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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