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)-gamma, 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-gamma+CD4+ cells (P = 0.01). The percentage of CD8+IFN-gamma+ 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-gamma/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-gamma 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.
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)-gamma, 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-gamma+CD4+ cells (P = 0.01). The percentage of CD8+IFN-gamma+ 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-gamma/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-gamma 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.
Authors: Stephanie Lovinsky-Desir; Robert Ridder; David Torrone; Christina Maher; Surinder Narula; Melissa Scheuerman; David Merle; Meyer Kattan; Emily DiMango; Rachel L Miller Journal: Clin Epigenetics Date: 2014-05-22 Impact factor: 6.551