TRYPTOPHAN-METABOLISM IN CHRONIC INFLAMMATORY LUNG-DISEASE

Induction of indoleamine 2,3-dioxygenase (IDO), an enzyme expressed by mononuclear phagocytes and some fibroblast cell lines in response to interferon-gamma, leads to enhanced degradation of tryptophan to kynur enine, Because inflammatory lung diseases are generally associated wit h activation of pulmonary macrophages, we investigated tryptophan meta bolism in patients with interstitial lung disease by measuring circula ting levels of tryptophan and kynurenine in peripheral blood and by me asuring the IDO activity of bronchoalveolar cells. IDO activities were increased for bronchoalveolar lavage (BAL) cells obtained from patien ts with interstitial lung disease (115.4 +/- 30.4, n = 37) when compar ed with BAL cells from normal subjects (15.2 +/- 7.4, n = 14; p < 0.05 ), and messenger RNA for IDO was present in BAL cells from patients wi th interstitial disease but was not present in BAL cells from normal v olunteer subjects. Patients with inflammatory lung disease also had de creased tryptophan and increased kynurenine concentrations in serum. T he ratio of serum tryptophan levels to serum kynurenine levels was sig nificantly depressed for patients with idiopathic pulmonary fibrosis ( 18.4 +/- 1.7, n = 29; p < 0.0001), patients with fibrosing alveolitis associated with collagen vascular disease (13.1 +/- 1.6, n = 18; p < 0 .0001), or patients with sarcoidosis (21.0 +/- 1.1, n = 50; p < 0.0001 ), as compared with the ratio for normal subjects (31.8 +/- 2.3, n = 1 8). Patients with fibrotic disease had the highest levels of BAL cell IDO activity, and patients with collagen vascular disease associated f ibrosing alveolitis had the most depressed levels of serum tryptophan and the greatest elevations in serum kynurenine, Measurement of trypto phan and kynurenine concentrations in serum may provide a useful measu re of disease activity in chronic inflammatory parenchymal lung diseas es such as sarcoidosis and idiopathic pulmonary fibrosis.