Role of CD14 in hemorrhagic shock-induced alterations of the monocyte tumor necrosis factor response to endotoxin.
OBJECTIVE
To determine if the shock-induced alterations in whole blood monocyte tumor necrosis factor (TNF) response are mediated by the CD14 receptor.


METHODS
Prospective controlled animals experiments.


METHODS
New Zealand White rabbits (n = 15) were subjected to hemorrhage and resuscitation. Blood samples obtained before shock and 24, 72, and 120 hours after shock were stimulated with lipopolysaccharide in the presence or absence of the anti-CD14 monoclonal antibody, 63D3. Tumor necrosis factor was assayed using L929 cells.


RESULTS
There are no detectable TNF activity in unstimulated blood. The CD14 inhibition resulted in a 55% reduction in baseline TNF activity. After shock, there was a marked increase in TNF activity with lipopolysaccharide stimulation. Addition of 63D3 resulted in a dose-dependent 95% reduction in TNF activity at 24 and 72 hours after shock, (p < 0.05).


CONCLUSIONS
The enhanced whole blood monocyte TNF response after hemorrhage is CD14 dependent.
Nwariaku
F
F
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031, USA.
Sikes
P
P
Lightfoot
E
E
McIntyre
K
K
Mileski
W J
WJ
D000818:Animals; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D011446:Prospective Studies; D011817:Rabbits; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha