Smoking cessation and nicotine substitution modulate eicosanoid synthesis ex vivo in man

The effects of smoking cessation with and without nicotine substitution on prostaglandin E2, leukotriene B4, leukotriene E4, and thromboxane B2 synthesis ex vivo in man were investigated. Blood samples were obtained from 20 healthy non-smoking controls and from 30 healthy smoking volunteers before and 3, 7 and 14 days after smoking cessation. Half of the smokers used nicotine chewing gum as a substitution therapy. Urinary cotinine and trans-3'-hydroxycotinine as well as thiocyanate excretions were used as indicators for the use of nicotine chewing gum and smoking, respectively. Prostaglandin E2, leukotriene E4, and thromboxane B2 were measured from whole blood after calcium ionophore A23187 stimulation by direct radioimmunoassay and leukotriene B4 by RP-HPLC. Prostaglandin E2 and thromboxane B2 syntheses were about three times and leukotriene B4 and E4 syntheses four times higher in smokers than in controls. Three days after smoking cessation without nicotine substitution, levels were lowered significantly to about 70%, 80%, 45% and 60% of the initial values; and after 14 days to 55%, 80%, 45% and 50%, respectively. In the nicotine substitution group no significant decreases were seen during the two-week follow-up. The increased level of eicosanoid synthesis detected in smokers in this ex vivo study may contribute to the harmful cardiovascular effects of smoking. Long-term nicotine substitution might diminish the beneficial effects of smoking cessation due to the possible stimulatory effects of nicotine and cotinine on eicosanoid synthesis even in vivo.