Monocyte suppressing action of fenofibrate.
Since atherosclerosis has been proven to be an inflammatory disease, it is obvious that the proper treatment for dyslipidemia should not only correct lipid parameters but also inhibit inflammation. Monocytes and monocyte-derived proinflammatory cytokines are widely known to be involved in the formation and rupture of the atherosclerotic plaque. The aim of our study was to assess the effect of fenofibrate, a commonly used hypolipidemic drug, on the release of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) by monocytes from patients with combined hyperlipidemia. Fourteen patients with biochemically confirmed type IIb dyslipidemia who did not respond to a low-fat diet were treated with micronized fenofibrate for 1 month. The control group included 12 healthy, normolipidemic, age-matched subjects. To accurately evaluate the levels of the inflammatory cytokines, we excluded patients with any inflammatory disease. Monocytes were isolated from peripheral blood before and after the treatment. IL-1beta, IL-6 and MCP-1 release was measured by enzyme-linked immunosorbent assay (ELISA) after lipopolysaccharide stimulation. IL-1beta, IL-6 and MCP-1 levels were significantly higher in hyperlipidemic patients compared to the control (143.9 +/- 6.5 vs. 74.4 +/- 4.4 pg/ml; 8212 +/- 285 vs. 6110 +/- 170 pg/ml; 19.6 +/- 0.9 vs. 12.3 +/- 0.6 ng/ml, respectively). Thirty-day fenofibrate treatment decreased the release of IL-1beta by 43% (143.9 +/- 6.5 vs. 86.2 +/- 5.9 pg/ml), of IL-6 by 22% (8212 +/- 285 vs. 6330 +/- 234 pg/ml), and of MCP-1 by 29% (19.6 +/- 0.9 vs. 14.0 +/- 0.8 ng/ml). The evaluated cytokines were markedly elevated in patients with type IIb dyslipidemia. Effective fenofibrate therapy had a significant inhibitory effect on the release of monocyte-derived inflammatory cytokines.
Okopień
Bogusław
B
Department of Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland. mbkdokop@mp.pl
Kowalski
Jan
J
Krysiak
Robert
R
Łabuzek
Krzystof
K
Stachura-Kułach
Aldona
A
Kułach
Andrzej
A
Zieliński
Marek
M
Herman
Zbigniew S
ZS
D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D000960:Hypolipidemic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D011345:Fenofibrate