Regulation of whole blood tumor necrosis factor production upon endotoxin stimulation after severe blunt trauma.
BACKGROUND
Trauma has been recognized to be accompanied by alterations of leukocyte functions such as cytokine release. The regulatory principles involved in these changes are still poorly defined. To further characterize leukocyte function after multiple trauma, endotoxin-stimulated tumor necrosis factor (TNF) production of trauma patients' whole blood and a possible regulatory mechanism were studied.


METHODS
Endotoxin responsiveness in trauma patients (n = 18, Injury Severity Score = 24 +/- 7) was assayed ex vivo using a whole blood model. TNF release and TNFalpha mRNA levels were determined during a 14-day period. Furthermore, the influence of patients' sera on whole blood TNF production was evaluated.


RESULTS
The capacity of trauma patients' whole blood to produce TNF was reduced for 2 to 6 days after trauma and was equally evident for both TNF release and TNFalpha mRNA levels. The reduction of TNF coincides with the appearance of an inhibitory activity for TNF production in trauma patients' sera. No correlation was found between the inhibitory activity and soluble TNF receptors, endotoxin-neutralizing molecules, inhibitory cytokines (interleukin 10 and transforming growth factor beta), or prostaglandins.


CONCLUSIONS
Major trauma leads to the appearance of a circulating inhibitory activity for TNF synthesis that may potentially contribute to an anti-inflammatory response in patients with multiple trauma. The elucidation of its structural and functional properties may contribute to the understanding of the pathogenesis of severely injured patients.
Majetschak
M
M
Department of Trauma Surgery, University Hospital Essen, Germany.
Flach
R
R
Heukamp
T
T
Jennissen
V
V
Obertacke
U
U
Neudeck
F
F
Schmit-Neuerburg
K P
KP
Schade
F U
FU
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016971:Citrobacter freundii; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006400:Hematocrit; D006801:Humans; D015601:Injury Severity Score; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D014949:Wounds, Nonpenetrating / Q000097:blood / Q000276:immunology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha