Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F(2)-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 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.

Nyckelord

Aged

Aging/*metabolism

Antioxidants/metabolism

Biological Markers/blood/urine

C-Reactive Protein/metabolism

Cohort Studies

Cytokines/metabolism

Dinoprost/analogs & derivatives/*biosynthesis/urine

F2-Isoprostanes/*biosynthesis

Humans

Inflammation/etiology

Interleukin-6/*biosynthesis/blood

Longitudinal Studies

Male

Oxidative Stress

Prostaglandin-Endoperoxide Synthases/metabolism

Smoking/*adverse effects

Smoking Cessation

Time Factors

Tocopherols/blood

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