TY - JOUR
T1 - Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design
AU - van der Sluijs, Koenraad F.
AU - van de Pol, Marianne A.
AU - Kulik, Wim
AU - Dijkhuis, Annemiek
AU - Smids, Barbara S.
AU - van Eijk, Hetty W.
AU - Karlas, Jos A.
AU - Molenkamp, Richard
AU - Wolthers, Katja C.
AU - Johnston, Sebastian L.
AU - van der Zee, Jaring S.
AU - Sterk, Peter J.
AU - Lutter, René
AU - AUTHOR GROUP
AU - Berger, Marieke
AU - Fens, Niki
AU - Yick, David
AU - Wagener, Ariane H.
AU - Amelink, Marijke
AU - Reesink, Herre J.
AU - Bresser, Paul
AU - Kunst, Peter W. A.
AU - Venekamp, Lisette N.
AU - Majoor, Christof J.
AU - van Steenwijk, Reindert P.
AU - Jonkers, René E.
PY - 2013
Y1 - 2013
N2 - 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. To determine whether IDO activity differs between patients with allergic asthma and healthy individuals before and after rhinovirus infection. 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. 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). 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
AB - 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. To determine whether IDO activity differs between patients with allergic asthma and healthy individuals before and after rhinovirus infection. 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. 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). 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
U2 - https://doi.org/10.1136/thoraxjnl-2013-203728
DO - https://doi.org/10.1136/thoraxjnl-2013-203728
M3 - Article
C2 - 23882022
SN - 0040-6376
VL - 68
SP - 1122
EP - 1130
JO - Thorax
JF - Thorax
IS - 12
ER -