title: 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 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.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, , Amsterdam, The Netherlands.
authors.forename: Koenraad F
authors.initials: KF
authors.lastname: van der Sluijs
authors.forename: Marianne A
authors.initials: MA
authors.lastname: van de Pol
authors.forename: Wim
authors.initials: W
authors.lastname: Kulik
authors.forename: Annemiek
authors.initials: A
authors.lastname: Dijkhuis
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Smids
authors.forename: Hetty W
authors.initials: HW
authors.lastname: van Eijk
authors.forename: Jos A
authors.initials: JA
authors.lastname: Karlas
authors.forename: Richard
authors.initials: R
authors.lastname: Molenkamp
authors.forename: Katja C
authors.initials: KC
authors.lastname: Wolthers
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Jaring S
authors.initials: JS
authors.lastname: van der Zee
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: René
authors.initials: R
authors.lastname: Lutter
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001944:Breath Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis; D018450:Disease Progression; D047150:Eosinophil Cationic Protein / Q000032:analysis; D004804:Eosinophils; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000032:analysis / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D010850:Picornaviridae Infections / Q000150:complications* / Q000821:virology; D011446:Prospective Studies; D017378:Quinolinic Acid / Q000032:analysis / Q000097:blood; D012229:Rhinovirus; D014364:Tryptophan / Q000032:analysis / Q000097:blood*; D055815:Young Adult; D062367:ortho-Aminobenzoates / Q000032:analysis / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D009569:Nitric Oxide; D007737:Kynurenine; D014364:Tryptophan; D009195:Peroxidase; D047150:Eosinophil Cationic Protein; D017378:Quinolinic Acid
keywords: Asthma Mechanisms; Lung Physiology; Viral infection