Document Detail


Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells.
MedLine Citation:
PMID:  15683457     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (suPAR) was measured by enzyme-linked immunosorbent assay in plasma and supernatants from unstimulated and phytohaemagglutinin and lipopolysaccharide-stimulated peripheral blood mononuclear cell (PBMC) cultures incubated for 24 h. The spontaneous and stimulated uPAR-release from PBMC cultures was enhanced 5 h after low-dose endotoxin (both P <0.05), but coadministration of rhIL-6 during low-dose endotoxaemia abolished this enhanced uPAR release. High-dose endotoxin increased plasma suPAR levels (P <0.001) whereas low-dose endotoxin, rhIL-6 or TNF-alpha did not influence uPAR release in vivo to such degree that a systemic effect on the plasma suPAR level was detectable. Even subclinical doses of endotoxin in vivo enhance the capacity of PBMC to release uPAR after incubation in vitro. The inhibitory effect of IL-6 on endotoxin-mediated uPAR-release in vitro suggests that IL-6 has anti-inflammatory effects on endotoxin-mediated inflammation.
Authors:
S R Ostrowski; P Plomgaard; C P Fischer; A S Steensberg; K Møller; G Høyer-Hansen; B K Pedersen; H Ullum
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of immunology     Volume:  61     ISSN:  0300-9475     ISO Abbreviation:  Scand. J. Immunol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-01     Completed Date:  2005-03-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0323767     Medline TA:  Scand J Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  197-206     Citation Subset:  IM    
Affiliation:
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dk
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MeSH Terms
Descriptor/Qualifier:
Adult
Endotoxemia / blood
Endotoxins / pharmacology*
Enzyme-Linked Immunosorbent Assay
Female
Humans
Interleukin-6 / blood,  immunology,  pharmacology*
Leukocyte Count
Leukocytes, Mononuclear / drug effects*,  immunology,  secretion
Lipopolysaccharides / immunology
Lymphocyte Activation / immunology
Lymphocyte Subsets
Male
Middle Aged
Receptors, Cell Surface / blood*,  immunology
Receptors, Urokinase Plasminogen Activator
Tumor Necrosis Factor-alpha / immunology
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Interleukin-6; 0/Lipopolysaccharides; 0/PLAUR protein, human; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; 0/Tumor Necrosis Factor-alpha

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