Evaluation of anti-inflammatory and anti-adhesive effects of heparins in human endotoxemia

Abstract

Sepsis results from a generalized inflammatory and pro-coagulant response to an infectious agent. Adhesion molecules and cytokines are of utmost importance for the development of early symptoms as well as the late sequela of endotoxemia. Heparin is widely known as an antithrombotic agent. But beyond its well-understood anticoagulant activity heparin is able to influence immunologic responses. In addition, in vitro experiments and animal studies have shown that heparin inhibits P-selectin and L-selectin mediated adhesion. Intravenous infusion of LPS into human volunteers provides a standardized model to study activation of inflammatory, pro-coagulant and adhesive cascades in humans. It was recently demonstrated that heparin blunts endotoxin-induced coagulation activation in a human LPS-model. As pro-coagulant and inflammatory processes are intricately linked in sepsis, we used this LPS-model to elucidate whether clinically applied doses of unfractionated (UFH) or low-molecular weight heparin (LMWH) are able to affect early inflammatory responses in low grade human endotoxemia.