A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors

Inflamm Res. 1996 Feb;45(2):68-74. doi: 10.1007/BF02265118.


In this study, PGE2 levels in lipopolysaccharide (LPS)-challenged human whole blood and TxB2 levels following blood coagulation were measured as biochemical index for cyclooxygenase (Cox)-2 and Cox-1 activity respectively. Incubation of human mononuclear cells isolated from whole blood with LPS (100 mu g/mL) induced a time-dependent increase in the expression of Cox-2 protein (>100 fold at 24 hr). This is associated with increases in PGE2 production and free arachidonate release in the plasma. Cox-1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS. Most non-steroidal anti-inflammatory drugs (NSAIDs) are more potent at inhibiting Cox-1 than Cox-2. Five experimental compounds CGP-28238, Dup-697, NS-398, SC-58125 and L-745,337, have a greater selectivity for Cox-2. Indomethacin at a single oral dose (25 mg) inhibited approximately 90% the whole blood Cox-2 and Cox-1 activities ex vivo in healthy subjects. These results support the use of this assay to assess the biochemical efficacy of selective Cox-2 inhibitors in clinical trials.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Arachidonic Acid / metabolism
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dinoprostone / biosynthesis
  • Female
  • Humans
  • Indomethacin / pharmacology
  • Lipopolysaccharides / pharmacology
  • Male
  • Thromboxane B2 / biosynthesis


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Lipopolysaccharides
  • Arachidonic Acid
  • Thromboxane B2
  • Dinoprostone
  • Indomethacin