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T-cell cytokine profiles are altered in childhood asthma exacerbation
Authors:Czarina  CALDERON  Luis  RIVERA  Paul  HUTCHINSON  Hayat  DAGHER  Elmer  VILLANUEVA  Reena  GHILDYAL  Philip G.  BARDIN AND Nicholas J.  FREEZER
Affiliation:Department of Respiratory and Sleep Medicine and Centre for Inflammatory Diseases, Monash University and Medical Centre, Melbourne, Victoria, Australia
Abstract:Background and objective:   Stable asthma is characterized by the production of Th2 cytokines, although Th1 cytokines may play a key role in aspects such as airway hyper-responsiveness. This study explored cytokine profiles associated with asthma exacerbation.
Methods:   Intracellular T-cell cytokine production was measured in 16 children with acute severe asthma (emergency department), after convalescence (6 weeks, n  = 13), with stable disease (after 6 months, n  = 7) and in 14 age-matched hospital controls. Flow cytometry was used to identify CD4+ and CD8+ cells and to quantify intracellular T-cell production of the cytokines interferon (IFN)-γ, IL-4 and IL-13. Cytokine production was compared using analysis of variance and random-effects generalized linear models and associations were examined using Pearson's correlation.
Results:   Cytokine production was evident in CD4+ and CD8+ cells, and compared with asthmatic children, non-asthmatics had a higher percentage of IFN-γ+CD4+ cells ( P  = 0.01). The percentage of CD8+IFN-γ+ cells was increased in the convalescent phase compared with acute ( P  = 0.009) and stable asthma ( P  = 0.004). IL-4+ cells were not significantly altered. IL-13 levels were higher in acute disease than in stable asthma ( P  = 0.009 in CD4+ cells) and IFN-γ/IL-13 ratios indicated a Th2 profile during exacerbation ( P  = 0.005 in CD4+ cells).
Conclusions:   IL-13, rather than IL-4, may play a pro-inflammatory role during acute severe asthma, whereas IFN-γ responses were associated with recovery from acute severe asthma. These results suggest that altered T-cell cytokine profiles may contribute to the pathogenesis of and recovery from asthma exacerbations.
Keywords:asthma    cytokine    exacerbation    IL-4    IL-13    interferon-γ    Th1/Th2
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