title: Gemfibrozil reduces release of tumor necrosis factor-alpha 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)-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.
authors.affiliation: 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
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Zhao
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Ye
authors.forename: Hong-Nian
authors.initials: HN
authors.lastname: Zhou
authors.forename: Sai
authors.initials: S
authors.lastname: Nie
authors.forename: Quan-Zhong
authors.initials: QZ
authors.lastname: Li
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D015248:Gemfibrozil