Gemfibrozil reduces release of tumor necrosis factor-α in peripheral blood mononuclear cells from healthy subjects and patients with coronary heart disease

Abstract

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)-α 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 (2×10 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-α was measured by an enzyme-linked immunosorbent assay (ELISA). Results: Spontaneous release of TNF-α 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-α 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-α secretion in both groups. Compared with that incubated with Ang II (10 −6 mol/l) alone, release of TNF-α 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-α secretion in both groups ( P<0.05). Conclusions: Our data demonstrated that gemfibrozil reduced release of TNF-α 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.