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.


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-1beta, IL-6, IL-8, and monocyte chemoattractant protein-1) as well as thrombin generation (prothrombin activation fragments F(1+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.
Birjmohun
Rakesh S
RS
Academic Medical Center of Amsterdam, Department of Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
van Leuven
Sander I
SI
Levels
Johannes H M
JH
van 't Veer
Cornelis
C
Kuivenhoven
Jan Albert
JA
Meijers
Joost C M
JC
Levi
Marcel
M
Kastelein
John J P
JJ
van der Poll
Tom
T
Stroes
Erik S G
ES
D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D007275:Injections, Intravenous; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011516:Prothrombin; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D018932:Chemokine CCL2; D008076:Cholesterol, HDL; D004731:Endotoxins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D002097:C-Reactive Protein; D043303:Aryldialkylphosphatase