title: Leukocyte phosphodiesterase expression after lipopolysaccharide and during sepsis and its relationship with HLA-DR expression.
abstract: Phosphodiesterases (PDEs) may modulate inflammatory pathways, but PDE expression is poorly documented in humans with sepsis. Using quantitative PCR on whole blood leukocytes, we characterized PDE mRNA expression in healthy volunteers (n= 20), healthy volunteers given lipopolysaccharide (LPS;n= 18), and critically ill patients with (n= 20) and without (n= 20) sepsis. PDE4B protein expression was also studied in magnetic-activated cell sorting (MACS)-isolated CD15+neutrophils (from 7 healthy volunteers, 5 patients without and 5 with sepsis). We studied relationships between PDE expression, HLA-DR (mRNA and expression on CD14+monocytes), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 levels. LPS administration in volunteers was associated with increases in PDE4B and PDE4D and decreases in PDE4A and PDE7A mRNAs. The observed global down-regulation of the HLA-DR complex was correlated with PDE7A. Critically ill patients had lower TNF-α/IL-10 mRNA ratios than the volunteers had and global down-regulation of the HLA-DR complex. Septic patients had persistently lower mRNA levels of PDE7A, PDE4A, and 4B (also at a protein level) and decreasing levels of PDE4D over time. Low PDE4D mRNA levels correlated negatively with HLA-DMA and HLA-DMB. LPS administration and sepsis are, therefore, associated with different PDE mRNA expression patterns. The effect of PDE changes on immune dysfunction and HLA-DR expression requires further investigation.
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lelubre
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Hayfa
authors.initials: H
authors.lastname: Medfai
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Israa
authors.initials: I
authors.lastname: Akl
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.|Nijmegen Centre for Infectious Diseases, Nijmegen, The Netherlands.
authors.forename: Jenneke
authors.initials: J
authors.lastname: Leentjens
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.|Nijmegen Centre for Infectious Diseases, Nijmegen, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.|Nijmegen Centre for Infectious Diseases, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Department of Intensive Care, Intercommunale de Santé Publique du Pays de Charleroi, CHU de Charleroi, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Biston
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.|Department of Intensive Care, Intercommunale de Santé Publique du Pays de Charleroi, CHU de Charleroi, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Piagnerelli
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Vanhaeverbeek
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Uzureau
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium; and jlvincent@intensive.org.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.affiliation: Laboratory of Molecular Parasitology, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Vanhamme
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Belgium.
authors.forename: Karim Zouaoui
authors.initials: KZ
authors.lastname: Boudjeltia
mesh_terms: D016022:Case-Control Studies; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D018805:Sepsis / Q000503:physiopathology*
chemical_list: D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D010727:Phosphoric Diester Hydrolases
keywords: critically ill; cytokines; immune dysfunction; neutrophil