Thorax · 2013
Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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van der Sluijs Koenraad F, van de Pol Marianne A, Kulik Wim, Dijkhuis Annemiek, Smids Barbara S, van Eijk Hetty W, Karlas Jos A, Molenkamp Richard, Wolthers Katja C, Johnston Sebastian L, van der Zee Jaring S, Sterk Peter J, Lutter René, RESOLVE research team
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAsthmaBiomarkersBreath TestsBronchoalveolar Lavage FluidCase-Control StudiesCytokinesDisease ProgressionEosinophil Cationic ProteinEosinophilsFemaleHumansIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineMaleNitric OxidePeroxidasePicornaviridae InfectionsProspective StudiesQuinolinic AcidRhinovirusTryptophanYoung Adultortho-Aminobenzoates