Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F2-isoprostane formation in elderly men

Atherosclerosis. 2005 Jul;181(1):201-7. doi: 10.1016/j.atherosclerosis.2004.11.026. Epub 2005 Apr 26.


The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F(2alpha) (PGF(2alpha)) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha)), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF(2alpha) (an F(2)-isoprostane, indicator of oxidative stress), and serum alpha-tocopherol were quantified in a population-based sample (n = 642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF(2alpha), P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF(2alpha) was increased (P < 0.01) and alpha-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF(2alpha), IL-6 and 8-iso-PGF(2alpha) compared non-smokers. This is the first study to show that smokers have increased PGF(2alpha) formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / metabolism*
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Biomarkers / urine
  • C-Reactive Protein / metabolism
  • Cohort Studies
  • Cytokines / metabolism
  • Dinoprost / analogs & derivatives
  • Dinoprost / biosynthesis*
  • Dinoprost / urine
  • F2-Isoprostanes / biosynthesis*
  • Humans
  • Inflammation / etiology
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / blood
  • Longitudinal Studies
  • Male
  • Oxidative Stress
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Smoking / adverse effects*
  • Smoking Cessation
  • Time Factors
  • Tocopherols / blood


  • Antioxidants
  • Biomarkers
  • Cytokines
  • F2-Isoprostanes
  • Interleukin-6
  • 8-epi-prostaglandin F2alpha
  • C-Reactive Protein
  • Dinoprost
  • Prostaglandin-Endoperoxide Synthases
  • Tocopherols