High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans

Objective - Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in humans. In the present study, we evaluated whether there is a relation between HDL and sensitivity toward a low-dose endotoxin challenge. Methods and Results - Thirteen healthy men with genetically determined isolated low HDL cholesterol (averaging 0.7 +/- 0.1 mmol/L) and 14 age- and body weight-matched healthy men with normal/high HDL cholesterol levels (1.9 +/- 0.4 mmol/L) were challenged with low-dose endotoxin intravenously (1 ng/kg body weight). The incidence and severity of endotoxin-associated clinical symptoms was increased in the low HDL group. Accordingly, both the inflammatory response (tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-8, and monocyte chemoattractant protein-1) as well as thrombin generation (prothrombin activation fragments F1+2) were significantly increased in the low HDL group on endotoxin challenge. Conclusions - Low HDL in healthy males is associated with increased sensitivity toward inflammatory stimuli as reflected by enhanced inflammatory and coagulation responses on endotoxin challenge. These antiinflammatory effects of HDL in humans may lend further support to HDL-increasing interventions, particularly in proinflammatory conditions, such as acute coronary syndromes.