Evaluation of antiinflammatory and antiadhesive effects of heparins in human endotoxemia
作者:
Ulla Derhaschnig,
Thomas Pernerstorfer,
Marteen Knechtelsdorfer,
Ursula Hollenstein,
Simon Panzer,
Bernd Jilma,
期刊:
Critical Care Medicine
(OVID Available online 2003)
卷期:
Volume 31,
issue 4
页码: 1108-1112
ISSN:0090-3493
年代: 2003
出版商: OVID
关键词: heparin;endotoxin;inflammation;cytokines;adhesion molecules
数据来源: OVID
摘要:
ObjectiveCytokines and adhesion molecules have a decisive role in the development of early inflammatory response as well as the late sequelae of sepsis. Because L-selectin-deficient mice are protected from lethal endotoxemia, blockade of L-selectin may provide a useful therapeutic option in human sepsis. Heparin has immunomodulatory properties and effectively inhibits L- and P-selectin bindingin vitro. We therefore investigated whether clinically applied doses of unfractionated or low-molecular-weight heparin affect early inflammatory response in human endotoxemia.DesignThe study was randomized, double-blinded, placebo-controlled, in three parallel groups consisting of 30 healthy male volunteers.SettingUniversity medical center.InterventionsAll subjects received a 2-ng/kg intravenous bolus of lipopolysaccharide and 10 mins later unfractionated heparin, low-molecular-weight heparin, or placebo as bolus primed continuous infusion for 6 hrs.Measurements and Main ResultsLipopolysaccharide infusion induced similar increases of tumor necrosis factor-&agr;, interleukin-6, interleukin-8, C-reactive protein, and soluble E-selectin levels in all treatment groups. CD11b expression increased by approximately 400%, but L-selectin decreased by 41% in the placebo arm 6 hrs after lipopolysaccharide infusion. Interestingly, both heparins (in particular unfractionated heparin) decreased L-selectin down-regulation as compared with placebo. Similarly, the decrease in lymphocyte counts was significantly less in the unfractionated heparin group during the first 24 hrs (p< .05 vs. placebo)ConclusionsHeparins displayed little effects on cytokine production and endothelial cell activation in endotoxemia. Of note, however, unfractionated heparin reduced L-selectin down-regulation and lymphocytopenia. These could present novel mechanisms of action of unfractionated heparin.
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