Gemfibrozil reduces release of tumor necrosis factor-alpha in peripheral blood mononuclear cells from healthy subjects and patients with coronary heart disease.
BACKGROUND
Inflammatory process plays an important role in the pathogenesis of coronary heart disease (CHD). With the growing use of gemfibrozil and other fibrates, their anti-inflammatory effects have been noted. But little is known about the effect of gemfibrozil on tumor necrosis factor (TNF)-alpha secretion in peripheral blood mononuclear cells (PBMC) from patients with coronary heart disease.


METHODS
PBMC were obtained from CHD patients (n=16) and healthy controls (n=13). PBMC (2x10(6) cells/ml) were cultured in 24-well plates with or without Ang II (10(-8), 10(-7), 10(-6) mol/l), or Ang II (10(-6) mol/l) plus gemfibrozil (10(-6), 10(-5), 10(-4) mol/l). After 24-h incubation, the supernatants were separated, and TNF-alpha was measured by an enzyme-linked immunosorbent assay (ELISA).


RESULTS
Spontaneous release of TNF-alpha was 299.2+/-110.7 pg/ml in PBMC from CHD patients and 179.3+/-78.2 pg/ml in PBMC from control subjects (P<0.05). Incubated with Ang II (10(-8), 10(-7), 10(-6) mol/l), TNF-alpha secretion was 307.7+/-141.8, 318.9+/-135.6, 328.6+/-123.9 pg/ml in PBMC from CHD patients, and 225.3+/-135.4, 224.1+/-141.0,218.7+/-134.8 pg/ml in PBMC from control subjects, respectively. Ang II did not significantly trigger TNF-alpha secretion in both groups. Compared with that incubated with Ang II (10(-6) mol/l) alone, release of TNF-alpha intervened by gemfibrozil (10(-6),10(-5),10(-4) mol/l) decreased to 279.4+/-132.2, 268.0+/-132.7, 226.6+/-102.7 pg/ml in PBMC from CHD patients, and 177.6+/-94.4, 156.1+/-69.4, 105.3+/-52.7 pg/ml in the control group, respectively. Gemfibrozil (10(-5),10(-4) mol/l) significantly inhibited TNF-alpha secretion in both groups (P<0.05).


CONCLUSIONS
Our data demonstrated that gemfibrozil reduced release of TNF-alpha in PBMC both from CHD patients and controls. This effect may partially be relevant to the clinical benefits of gemfibrozil in the treatment of dyslipidemia and atherosclerosis.
Zhao
Shui-Ping
SP
Department of Cardiology, The Second XiangYa Hospital, Central South University, Middle Renmin Road No. 86, ChangSha, Hunan 410011, People's Republic of China. ZhaoSP@public.cs.hn.cn
Ye
Hui-Jun
HJ
Zhou
Hong-Nian
HN
Nie
Sai
S
Li
Quan-Zhong
QZ
D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D015248:Gemfibrozil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007677:Kidney Function Tests; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008111:Liver Function Tests; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D015248:Gemfibrozil