Peripheral blood mononuclear cell production of interleukin-8 and IL-8-dependent neutrophil function in hypercholesterolemic patients.
Interleukin-8 is a cytokine produced by mononuclear cells that is involved in polymorphonuclear neutrophil leukocyte (PMN) recruitment and activation. Several studies have previously demonstrated a leukocyte activation during hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been found to play a role in the prevention of atherothrombotic disease. The purpose of this study was to determine interleukin-8 (IL-8) mRNA expression and ex vivo production from peripheral blood mononuclear cells (PBMCs) and IL-8-dependent PMN activation of hypercholesterolemic (HC) patients with respect to normocholesterolemic (NC) subjects. Using Northern blot analysis, we found a four- and threefold increase in the amount of IL-8 transcript in PBMC from HC patients, in unstimulated and LPS stimulated cultures, respectively. A specific immunoassay showed a correspondingly significant increase of IL-8 immunoactivity in the conditioned medium of PBMC from HC subjects as compared with controls (unstimulated PBMC: 15 +/- 4 vs. 4.2 +/- 3 ng/ml; P < 0.0001; LPS stimulated PBMC: 65.3 +/- 8 vs. 36.6 +/- 9 ng/ml; P < 0.0001). PMN of HC patients stimulated with IL-8 showed a reduced elastase release with respect to NC subjects before physiological granule release after f-Met-Leu-Phe (fMLP) treatment. These results indicate an upregulation of the IL-8 system in dyslipidemic patients and provide evidence for ongoing in vivo IL-8-dependent PMN activation during hypercholesterolemia.
Porreca
E
E
Department of Internal Medicine, University of Chieti, Medical School, Italy.
Sergi
R
R
Baccante
G
G
Reale
M
M
Orsini
L
L
Febbo
C D
CD
Caselli
G
G
Cuccurullo
F
F
Bertini
R
R
D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019272:Leukocyte Elastase / Q000096:biosynthesis / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*
D016209:Interleukin-8; D012333:RNA, Messenger; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002784:Cholesterol; D019272:Leukocyte Elastase