The activity of the immunoregulatory enzyme indoleamine 2,3-dioxygenase is decreased in smokers

Abstract

Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the degradation of the essential amino acid tryptophan (trp) to its main metabolite kynurenine (kyn), suppresses T cell activity. Smoking has marked immunomodulatory effects, above all immunosuppressive, causing a reduction in the levels of immunoglobulins and an increased risk of infections. The immunostimulatory effects of smoking are manifested, for example, in increased autoantibody production. We sought to establish whether IDO activity is involved in the immunomodulatory effects of smoking. To this end we measured the ratio of kyn to trp, reflecting IDO activity, by reverse-phase high-performance liquid chromatography (HPLC) in 784 (464 female, 230 male) subjects of a population-based sample of the adult Finnish population. Serum cotinine concentration as an indicator of active smoking was measured in the patients by radioimmunoassay and detailed data gathered on smoking habits. IDO activity was lower in smokers in this population-based sample compared with non-smokers when active smoking was classified according to serum cotinine concentration or history of smoking habits. Moreover, serum IDO activity correlated inversely with serum cotinine concentration. In conclusion, the activity of the IDO enzyme is decreased in smoking subjects, and the reduction in IDO-dependent immunosuppression could thus be responsible for the known immunostimulatory effects of smoking.