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(The FASEB Journal. 2001;15:1941-1952.)
© 2001 FASEB

High density lipoproteins reduce organ injury and organ dysfunction in a rat model of hemorrhagic shock

GILLIAN W. COCKERILL1, MICHELLE C. MCDONALD*, HELDER MOTA-FILIPE{dagger}, SALVATORE CUZZOCREA{dagger}, NORMAN E. MILLER** and CHRISTOPH THIEMERMANN*

Experimental Therapeutics and
* Experimental Medicine and Nephrology, and
** Cardiovascular Biochemistry, St. Bartholomew’s and the Royal London SMD, Queen Mary and Westfield College, London EC1M 6BQ, UK; and
{dagger} Institute of Pharmacology, School of Medicine, University of Messina, Messina 98123, Italy

1Correspondence: Experimental Therapeutics, St. Bartholomew’s and the Royal London SMD, Queen Mary and Westfield College, Charterhouse Square, London EC1M 6BQ, UK. E-mail: g.w.cockerill{at}mds.qmw.ac.uk

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 measuring their ability to prevent neutrophil adhesion and transmigration in vitro. Treatment of human endothelial cell cultures with physiologic concentrations of HDLs inhibited neutrophil binding by 68 ± 5.9% (mean and SE, n=6, P<0.05) and neutrophil transmigration by 48.7 ± 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 trauma 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 to 50 mmHg) and 1 min before resuscitation showed attenuation of the increases 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 that received HDLs. Human HDLs attenuate the MODS associated with ischemia and reperfusion injury after hemorrhagic shock in rats.—Cockerill, G. W., McDonald, M. C., Mota-Filipe, H., Cuzzocrea, S., Miller, N.E., Thiemermann, C. High density lipoproteins reduce organ injury and organ dysfunction in a rat model of hemorrhagic shock.


Key Words: cytokines • chemokines • intercellular adhesion molecule 1 • interleukin 8 • multiple organ failure




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