Gw. Cockerill et al., High density lipoproteins reduce organ injury and organ dysfunction in a rat model of hemorrhagic shock, FASEB J, 15(11), 2001, pp. 1941-1952
High density lipoproteins (HDLs) inhibit the cytokine-induced expression of
endothelial cell adhesion molecules both in vitro and in vivo. We examined
the ability of HDLs to mediate a functional anti-inflammatory effect by me
asuring their ability to prevent neutrophil adhesion and transmigration in
vitro. Treatment of human endothelial cell cultures with physiologic concen
trations of HDLs inhibited neutrophil binding by 68 +/-5.9% (mean and SE, n
=6, P<0.05) and neutrophil transmigration by 48.7<plus/minus>6.7% (n=8, P<0
.05). We then examined the effect of HDLs on inflammatory infiltration and
subsequent multiple organ dysfunction syndrome (MODS), associated with trau
ma in a rat model of hemorrhagic shock. Rats given human HDLs (80 mg apo A-
I/kg, i.v.) 90 min after hemorrhage (which reduced mean arterial pressure t
o 50 mmHg) and 1 min before resuscitation showed attenuation of the increas
es in the serum levels of markers of MODS normally observed in this model.
Severe disruption of the architecture of tissues and the extensive cellular
infiltration into those tissues were also largely inhibited in animals tha
t received HDLs. Human HDLs attenuate the MODS associated with ischemia and
reperfusion injury after hemorrhagic shock in rats.