| Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats. | |
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MedLine Citation:
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PMID: 1386478 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention. Interleukin-1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis. The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin-1 receptor antagonist (IL-1ra) against polymicrobial gram-negative septicemia in rats. METHODS: Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture (CLP). After 3 hours rats received either IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of vehicle intravenously for 24 hours. Heart rate, respirations, mean arterial blood pressure, and temperature were recorded at frequent intervals, and survival was assessed for 30 hours after CLP. RESULTS: There were no differences in vital signs between groups at baseline or before treatment, and all animals appeared ill with huddled posture, piloerection, and hyperventilation. Twenty-four hours after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly improved (71% vs 20%, p less than 0.05). CONCLUSIONS: IL-1ra lessens the acute hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by CLP in rats. These data suggest that IL-1 receptor blockade may be an important new treatment strategy against overwhelming bacterial sepsis. |
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Authors:
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H R Alexander; G M Doherty; D J Venzon; M J Merino; D L Fraker; J A Norton |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Surgery Volume: 112 ISSN: 0039-6060 ISO Abbreviation: Surgery Publication Date: 1992 Aug |
Date Detail:
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Created Date: 1992-08-28 Completed Date: 1992-08-28 Revised Date: 2010-03-24 |
Medline Journal Info:
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Nlm Unique ID: 0417347 Medline TA: Surgery Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 188-93; discussion 193-4 Citation Subset: AIM; IM |
Affiliation:
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Surgical Metabolism Section, National Cancer Institute, NIH, Bethesda, MD 20892. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cecum Gram-Negative Bacterial Infections / drug therapy*, pathology Infusions, Intravenous Interleukin-1 / metabolism Ligation Liver / drug effects, pathology Male Pilot Projects Punctures Rats Rats, Inbred F344 Receptors, Immunologic / antagonists & inhibitors* Receptors, Interleukin-1 Recombinant Proteins Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-1; 0/Receptors, Immunologic; 0/Receptors, Interleukin-1; 0/Recombinant Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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