Document Detail


Interleukin-10 blunts the human inflammatory response to lipopolysaccharide without affecting the cardiovascular response.
MedLine Citation:
PMID:  15699836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The objective of this study was to assess the efficacy of variations in dose and timing of administration of recombinant human IL-10 (rhIL-10) on inflammatory and cardiovascular responses in a human endotoxemia model of sepsis. DESIGN: The authors conducted a randomized, placebo-controlled, double-blind trial. SETTING: The study was conducted in a procedure room of an intensive-care unit. PARTICIPANTS: The study comprised 24 healthy male volunteers. INTERVENTIONS: Interventions consisted of intravenous administration of rhIL-10 at 1, 10, or 25 microg/kg either 2 mins or 2 hrs before Escherichia coli lipopolysaccharide (4 ng/kg) or placebo. MEASUREMENTS AND RESULTS: The placebo group receiving lipopolysaccharide alone demonstrated significant, time-dependent changes in vital signs, white blood cell counts, inflammatory cytokine/cortisol levels, and hemodynamic/cardiovascular (including echocardiographic) parameters over the duration of the study. rhIL-10, administered immediately before (concurrent) lipopolysaccharide resulted in decreased temperature and heart rate responses as well as decreased serum levels of proinflammatory cytokines (tumor necrosis factor-alpha, IL-6), IL-1 receptor antagonist, cortisol, and total leukocytes/neutrophils compared with lipopolysaccharide alone. Dose-dependent effects were absent. In contrast, rhIL-10 administration 2 hrs before endotoxin augmented the endotoxin-induced IL-beta and IL-1 receptor antagonist response. rhIL-10 failed to modulate major cardiovascular responses (cardiac output, stroke volume index, ejection fraction, peak systolic pressure/end-systolic volume ratio) to endotoxin in both study groups as assessed by echocardiography. CONCLUSION: Concurrent administration of rhIL-10 suppresses the human inflammatory/stress response but has no effect on the hemodynamic/cardiovascular response to endotoxin. Early administration of rhIL-10 can potentially augment elements of the cytokine inflammatory response to lipopolysaccharide. These findings suggest significant limitations of rhIL-10 as a potential immunomodulatory therapy for sepsis.
Authors:
Anand Kumar; Sergio Zanotti; Gene Bunnell; Kalim Habet; Ramon Añel; Alex Neumann; Mary Cheang; Charles A Dinarello; David Cutler; Joseph E Parrillo
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Critical care medicine     Volume:  33     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-08     Completed Date:  2005-03-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  331-40     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiovascular Disease and Critical Care Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Cytokines / blood*
Dose-Response Relationship, Drug
Double-Blind Method
Escherichia coli*
Hemodynamics / drug effects*
Humans
Inflammation / etiology,  physiopathology
Inflammation Mediators / blood
Interleukin-10 / administration & dosage*
Leukocyte Count
Lipopolysaccharides / toxicity*
Male
Recombinant Proteins / administration & dosage
Sepsis / drug therapy,  physiopathology*
Grant Support
ID/Acronym/Agency:
AI-15614/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators; 0/Lipopolysaccharides; 0/Recombinant Proteins; 130068-27-8/Interleukin-10

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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