Anti-inflammatory effects of the novel phosphodiesterase type 4 inhibitor CHF6001 on bronchoalveolar lavage lymphocytes from asthma patients

Abstract

Background: CHF6001 is a highly potent and selective phosphodiesterase type 4 inhibitor designed for inhaled administration, and has been shown to reduce the late asthmatic response. Lymphocyte numbers are increased in asthma patients, with TH2 cells being associated with eosinophilic inflammation, while TH1 and TH17 cells may play an important role in severe asthma. Aim: To evaluate the anti-inflammatory effects of CHF6001 and the corticosteroid, 17-BMP, on TH1, TH2 and TH17 cytokine release by bronchoalveolar lavage (BAL) lymphocytes from steroid naive mild (MA) and moderate to severe (SA) asthma patients. Method: BAL cells from 12 MA and 12 SA patients were treated with CHF6001 (0.1-1000nM) and/or 17-BMP (0.01-100nM), before T-cell receptor stimulation for 24 hrs. Levels of IL-2, IL-13, IL-17 and IFNγ were measured by ELISA. Results: CHF6001 inhibited IL-2, IFNγ and, to a lower extent, IL-17, but not IL-13, from MA and SA cells; the maximum levels of inhibition were similar in MA and SA (Table 1). Cytokine inhibition by 17-BMP was greater in MA cells than SA. CHF6001 had a greater effect than 17-BMP on IL-2 and IFNγ (Table 2). Combining CHF6001 with 17-BMP increased IFNγ inhibition. Conclusion: CHF6001 inhibits TH1 and TH17 cytokine production from lymphocytes obtained from moderate to severe asthma patients.