title: Development of an in vitro screening assay to test the antiinflammatory properties of dietary supplements and pharmacologic agents.
abstract: BACKGROUND
  Monocytes and macrophages are critical in atherosclerosis and on stimulation secrete proinflammatory, proatherogenic cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, which have been shown to be present in atherosclerotic lesions. The aim of this study was to develop a rapid in vitro screening assay to test the antiinflammatory effects of different compounds.
  
  
  RESULTS
  THP-1 cells (human monocytic cell line) were stimulated with different concentrations of lipopolysaccharide (LPS; 0 to 1000 microg/L) and for different times (4, 12, and 24 h), and the secretion of proinflammatory cytokines (IL-1, IL-6, and TNF-alpha) was assessed. TNF-alpha secretion was maximum at the lowest LPS concentration (100 microg/L) and at shortest duration of incubation (4 h). Maximum secretion of IL-1beta and IL-6 was achieved at 24 h with higher doses of LPS. Treatment of THP-1 with various test compounds such as dietary supplements (alpha-tocopherol, N-acetylcysteine, catechin and epigallocatechin gallate) as well as pharmacologic agents (statins, peroxisome proliferator-activated receptor-gamma agonists, and an angiotensin II receptor blocker) significantly inhibited LPS-stimulated TNF-alpha release.
  
  
  CONCLUSIONS
  The release of TNF-alpha after stimulation of THP-1 cells with LPS is a valid model system to test novel compounds for potential antiinflammatory effects.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology & Laboratory Medicine, University of California, Davis Medical Center, Sacramento, 95817, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Singh
authors.forename: James
authors.initials: J
authors.lastname: Tabibian
authors.forename: Senthil K
authors.initials: SK
authors.lastname: Venugopal
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha