Abstract
Background: Phosphatidylinositol 3-kinase delta (PI3Kδ) and Janus kinases (JAK) are both novel anti-inflammatory targets in COPD and asthma. However, very little is understood about the role these kinases play in pulmonary lymphocyte responses in these diseases.
Aims: To investigate if cytokines produced by pulmonary lymphocytes from COPD and severe asthma (SA) patients are dependent on PI3Kδ or JAK, and to compare the effects of inhibitors of these pathways with corticosteroids.
Methods: Bronchoalveolar lavage cells were isolated from patients with COPD (n=8), SA (n=11) and healthy non-smokers (HNS) (n=10). The cells were treated with inhibitors of PI3Kδ and JAK or dexamethasone before stimulation with antibodies against CD3 and CD28 to induce a T-cell receptor response. Levels of IFNγ, IL-13 and IL-17A were measured by ELISA.
Results: The level of IFNγ inhibition by dexamethasone was reduced in COPD compared to HNS cells (Table 1). JAK and PI3Kδ inhibitors reduced cytokine levels equally in the three groups.
Conclusions: Targeting PI3Kδ or JAK may prove effective in reducing T-cell controlled inflammatory responses in both COPD and SA patients.
- © 2013 ERS