Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs
Disease area: Airway diseases

Abstract

RationaleCD8 cells play a role in COPD pathogenesis. Glucocorticoids (GC) and phosphodiesterase 4 inhibitors (PDE4i) are established anti-inflammatory treatments. We studied the combined effects of GC with PDE4i on COPD CD8 cells.MethodsCD8 cells were treated with dexamethasone (dex) alone or in combination with roflumilast or GSK256066 prior to stimulation. Interleukin 2 (IL-2) and interferon gamma (IFNg) release were measured by ELISA.The combined effects of dex with PDE4i on mRNA levels of the GC inducible genes GILZ, MKP-1 and FKBP5 were measured using qRT-PCR.The combined effects of dex with PDE4i on nuclear translocation of key transcription factors were studied using immunofluorescence for p65, CREB and NFAT.ResultsDex inhibited IL-2 and IFNg release in a concentration dependent manner. The addition of PDE4i significantly enhanced the effect of dex in an additive fashion.Dex significantly increased transcription of GILZ, MKP-1 and FKBP-5. GSK256066 had no effect on GILZ or FKBP-5 but significantly increased transcription of MKP-1. There was some evidence to suggest that Dex and GSK256066 together synergistically enhanced transcription of MKP-1.Dex inhibited nuclear translocation of p65. GSK256066 increased CREB nuclear translocation. Neither dex nor GSK256066 affected NFAT nuclear translocation.ConclusionsThe combination of dexamethasone with PDE4 inhibitors results in an additive anti-inflammatory effect. This addition appears to be due to effects on different transcription factors. These findings may translate to enhanced clinical benefits with the combination of inhaled corticosteroids with PDE4i.

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Citations should be made in the following way:
S. Grundy, J. Plumb, M. Kaur, S. Lea, D. Singh (Manchester, United Kingdom). Additive anti-inflammatory effect of glucocorticoids and PDE4 inhibitors on COPD CD8 cells. Eur Respir J 2014; 44: Suppl. 58, 1515

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