Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway

Cancer Prev Res (Phila). 2009 Apr;2(4):322-9. doi: 10.1158/1940-6207.CAPR-09-0005. Epub 2009 Mar 31.


Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / drug effects*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Arachidonic Acid / metabolism
  • Celecoxib
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Female
  • Humans
  • Leukotriene E4 / urine*
  • Male
  • Middle Aged
  • Pneumonia / chemically induced
  • Pneumonia / urine
  • Prostaglandins E / metabolism*
  • Pyrazoles / pharmacology*
  • Signal Transduction
  • Smoking / adverse effects
  • Smoking / urine*
  • Sulfonamides / pharmacology*


  • Cyclooxygenase 2 Inhibitors
  • Prostaglandins E
  • Pyrazoles
  • Sulfonamides
  • Arachidonic Acid
  • Leukotriene E4
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • Celecoxib