Active smoking and a history of smoking are associated with enhanced prostaglandin F2α, interleukin-6 and F2-isoprostane formation in elderly men

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 F2α (PGF2α) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF2α (a major metabolite of PGF2α), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF2α (an F2-isoprostane, indicator of oxidative stress), and serum α-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-PGF2α, P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF2α was increased (P < 0.01) and α-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF2α, IL-6 and 8-iso-PGF2α compared non-smokers. This is the first study to show that smokers have increased PGF2α 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.