Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design

Abstract

Background Patients with allergic asthma have exacerbations which are frequently caused by rhinovirus infection. The antiviral tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is induced by interferon-γ and suppressed by Th2 mediators interleukin (IL)-4 and IL-13. We hypothesised that local IDO activity after viral airway infection is lower in patients with allergic asthma than in healthy controls. Objective To determine whether IDO activity differs between patients with allergic asthma and healthy individuals before and after rhinovirus infection. Methods Healthy individuals and patients with allergic asthma were experimentally infected with low-dose (10 TCID 50 ) rhinovirus 16. Blood, bronchoalveolar lavage fluid and exhaled breath condensate (for mass spectrometry by UPLC-MS/MS) were obtained before and after rhinovirus challenge. Results IDO activity was not induced by rhinovirus infection in either group, despite increases in cold scores. However, baseline pulmonary IDO activity was lower in patients with allergic asthma than in healthy individuals. In contrast, systemic tryptophan and its catabolites were markedly higher in patients with allergic asthma. Moreover, systemic quinolinic acid and tryptophan were associated with eosinophil cationic protein (r=0.43 and r=0.78, respectively) and eosinophils (r=0.38 and r=0.58, respectively) in bronchoalveolar lavage fluid and peak asthma symptom scores after rhinovirus challenge (r=0.53 and r=0.64, respectively). Conclusions Rhinovirus infection by itself induces no IDO activity, but the reduced pulmonary IDO activity in patients with allergic asthma at baseline may underlie a reduced control of viral infections. Notably, the enhanced systemic catabolism of tryptophan in patients with allergic asthma was strongly related to the outcome of rhinovirus challenge in asthma and may serve as a prognostic factor.

The Effect of Chinese Herbal Medicine Formula mKG on Allergic Asthma by Regulating Lung and Plasma Metabolic Alternations

“…It has been reported that systemic tryptophan and its catabolites relate to the severity of rhinovirus-induced asthma exacerbation in patients with allergic asthma [36]. In our study, a low level of l -tryptophan ( P14 ) was observed in the plasma of OVA-challenged mice, and this depletion of l -tryptophan ( P14 ) led to abnormalities of the energy metabolism.…”

Current and future biomarkers in allergic asthma

“…Due to the systemic involvement, asthma exacerbation can also be monitored or even predicted by urinary metabolites including arachidonic derivatives such as leukotrienes (184,185) and urinary trypsin inhibitor (186). Exacerbated allergic asthma is accompanied with increased BAL levels of quinolinic acid, tryptophan, ECP, eosinophils (187), decreased CD29 (32) and CD44 (188) on eosinophils and elevated CD203c expression on basophils, which decreases significantly during remission (101 (189). While early or mild conditions are well-reflected local biomarkers, it appears that moderate to severe disease conditions are even visible in the peripheral blood.…”

The Role of Dendritic Cells and Monocytes in the Maintenance and Loss of Respiratory Tolerance

“…The contribution of IDO in allergic airways disease in humans is an active area of study. In one study, IDO activity was significantly decreased in the BAL of patients with allergic asthma, providing a link between low IDO and airway hyperreactivity (19). …”