Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9017435 | Pulmonary Pharmacology & Therapeutics | 2005 | 6 Pages |
Abstract
Chronic obstructive pulmonary disease (COPD) is a common, progressive respiratory disease that causes great morbidity and mortality despite treatment. Tumor necrosis factor α (TNF-α) plays a central role as a pro-inflammatory cytokine in COPD. TNF-α release is markedly inhibited by phosphodiesterase type 4 (PDE4) inhibitors that have proven efficacious in COPD clinical trials. The aim of this study was to compare the in vitro activities of the novel selective PDE4 inhibitors CI-1044 compared to well-known PDE4 inhibitors, rolipram and cilomilast, and to the glucocorticoid dexamethasone at reducing lipopolysaccharide (LPS)-induced TNF-α release in whole blood from COPD patients and healthy subjects. In the whole blood from COPD patients pre-incubation with PDE4 inhibitors or dexamethasone resulted in a dose-dependent inhibition of LPS-induced TNF-α release with IC50 values of 1.3±0.7, 2.8±0.9 μM, higher to 10 μM and lesser than 0.03 μM for CI-1044, rolipram, cilomilast and dexamethasone, respectively. We observed a similar inhibition in the whole blood from healthy volunteers with, however, higher IC50 values. These results indicate that CI-1044 inhibits in vitro LPS-induced TNF-α release in whole blood from COPD patients better than rolipram and cilomilast and suggested that it could be a useful anti-inflammatory therapy in COPD.
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Authors
M. Ouagued, C.A.E. Martin-Chouly, G. Brinchault, C. Leportier-Comoy, A. Depincé, C. Bertrand, V. Lagente, C. Belleguic, M.P. Pruniaux,