Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design
Open Access
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 TCID50) 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.Keywords
This publication has 34 references indexed in Scilit:
- Frequent Detection of Respiratory Viruses without Symptoms: Toward Defining Clinically Relevant Cutoff ValuesJournal of Clinical Microbiology, 2011
- Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide*Critical Care Medicine, 2009
- Alterations of the Arginine Metabolome in AsthmaAmerican Journal of Respiratory and Critical Care Medicine, 2008
- Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 productionProceedings of the National Academy of Sciences, 2008
- Indoleamine 2,3-dioxygenase–dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse modelJournal of Allergy and Clinical Immunology, 2008
- Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cellsBlood, 2008
- Mechanisms of virus‐induced asthma exacerbations: state‐of‐the‐art. A GA2LEN and InterAirways documentAllergy, 2007
- Influenza‐Induced Expression of Indoleamine 2,3‐Dioxygenase Enhances Interleukin‐10 Production and Bacterial Outgrowth during Secondary Pneumococcal PneumoniaThe Journal of Infectious Diseases, 2006
- Asymptomatic atopy is associated with increased indoleamine 2,3‐dioxygenase activity and interleukin‐10 production during seasonal allergen exposureClinical & Experimental Allergy, 2004
- Inhibition of human herpes simplex virus type 2 by interferon γ and tumor necrosis factor α is mediated by indoleamine 2,3-dioxygenaseMicrobes and Infection, 2004