Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy

We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU dL-alpha-tocopherol daily, n = 64). After two years of therapy, we measured phorbol 12-myristate 13 -acetate- induced superoxide production of isolated neutrophils and of diluted whole blood by monitoring reduction of ferricytochrome c and luminol-enhanced peroxidase-catalyzed chemiluminescence. Plasma lipids and lipoproteins were not different between the two treatment groups. As expected, concentrations of alpha-tocopherol in plasma and in low-density lipoproteins were markedly elevated in the supplemented group compared to the placebo group (+ 120%, P <0.0001 and + 83%, P <0.0001, respectively). Consequently, resistance to in vitro oxidation of low-density lipoproteins (reflected by lag time of conjugated diene formation) was higher in the supplemented group than in the placebo group (+ 22%, P <0.0001). Superoxide generating capacity of neutrophils and superoxide production in diluted whole blood did not differ between α-tocopherol and placebo group. It is concluded that in chronic smoking long-term supranormal α-tocopherol intake does not reduce neutrophil superoxide-anion generating capacity, despite large increases in the concentrations of α-tocopherol in plasma and in low-density lipoproteins.