[Differential modulation of TLR2 and TLR4-induced TNF production by murin haemorrhagic shock].
OBJECTIVE
To investigate the influence of haemorrhagic shock in mice on ex vivo TNF production by whole blood cells (WBC) stimulated through Toll-like receptors (TLR) 4 and 2. STUDY DESIGN AND ANIMALS: Experimental study using BALB/c male mice.


METHODS
Haemorrhage (0,026+/-0,003 ml/g) by transparietal cardiac puncture under general anaesthesia. Measurement of left intraventricular pressure through a direct subcostal cardiac puncture. Possible restitution of shed blood volume (SBV) in retroorbital venous plexus, 60 minutes following haemorrhage. Lethal exsanguination 120 minutes following general anaesthesia (Control group), cardiac puncture (Sham group), blood sample (Haemorrhage group), or 60 minutes following SBV retransfusion (SBV group). Cultures (24 hours) of whole blood from the exsanguination, alone or with Escherichia coli endotoxin (LPS, TLR 4) or with heat-killed Staphylococcus aureus Cowan (SAC, TLR 2). Assessment of TNF levels in the cultures supernatant (Elisa).


RESULTS
Hemorrhage (approximately 30% of calculated blood volume) resulted in arterial hypotension (-50%) which was reversed by SBV retransfusion. TNF production by LPS-stimulated WBC was reduced by haemorrhage (approximately -50%) with or without SBV retransfusion. TNF production by SAC-stimulated WBC remained unchanged.


CONCLUSIONS
The reduction of proinflammatory cytokines production by WBC stimulated with pathogen-associated molecular patterns is not a generalized phenomenon following murin haemorrhagic shock. It depends on the used stimulus and studied signalling pathways.
Asehnoune
K
K
Service d'anesthésie-réanimation et unité propre de recherche de l'enseignement supérieur, équipe d'accueil (UPRES-EA 3540), hôpital de Bicêtre, 94275 Le Kremlin-Bicêtre cedex, France. karim.asehnoune@bct.ap-hp.paris
Moine
P
P
Fitting
C
C
Benhamou
D
D
Cavaillon
J-M
JM
Edouard
A
A
D000818:Animals; D001803:Blood Transfusion; D002478:Cells, Cultured; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000502:physiology*; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology; D013203:Staphylococcal Infections / Q000503:physiopathology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha