SMOKING CESSATION AND NICOTINE SUBSTITUTION MODULATE EICOSANOID SYNTHESIS EX-VIVO IN MAN

The effects of smoking cessation with and without nicotine substitutio n on prostaglandin E(2), leukotriene B-4, leukotriene E(4), and thromb oxane B-2 synthesis ex vivo in man were investigated. Blood samples we re obtained from 20 healthy non-smoking controls and from 30 healthy s moking volunteers before and 3, 7 and 14 days after smoking cessation. Half of the smokers used nicotine chewing gum as a substitution thera py. Urinary cotinine and trans-3'-hydroxycotinine as well as thiocyana te excretions were used as indicators for the use of nicotine chewing gum and smoking, respectively. Prostaglandin E(2), leukotriene E(4), a nd thromboxane B-2 were measured from whole blood after calcium ionoph ore A23187 stimulation by direct radioimmunoassay and leukotriene B-4 by RP-HPLC. Prostaglandin E(2) and thromboxane B-2 syntheses were abou t three times and leukotriene B-4 and E(4) syntheses four times higher in smokers than in controls. Three days after smoking cessation witho ut nicotine substitution, levels were lowered significantly to about 7 0%, 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 inc reased level of eicosanoid synthesis detected in smokers in this ex vi vo study may contribute to the harmful cardiovascular effects of smoki ng. Long-term nicotine substitution might diminish the beneficial effe cts of smoking cessation due to the possible stimulatory effects of ni cotine and cotinine on eicosanoid synthesis even in vivo.