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Anti-inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus-inducible cytokines.
Pharmacol Res Perspect 2016; 4(1):e00202PR

Abstract

Respiratory virus infections precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations, with most exacerbations due to rhinovirus infection. Both asthma and COPD exacerbations are not well controlled by steroid therapies, and there is a much research interest in finding improved therapies or combinations of therapies for controlling exacerbations. CHF6001 is a new, inhaled highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor. Using in vitro human bronchial epithelial cells (BEAS-2B), we investigated the potential anti-inflammatory effects of CHF6001 on rhinovirus (RV1B)-induced cytokines. Cytokine mRNA was measured by real-time PCR, while protein release was measured by ELISA. CHF6001 was used in a 7-point dose-response curve (1000-0.001 nmol/L) as a 1.5-h pretreatment prior to infection in comparison with roflumilast. Both roflumilast and CHF6001 reduced RV1B-induced IL-8, IL-29, IP-10, and RANTES mRNA and protein in a concentration-dependent manner. Generally, CHF6001 was 13- to 16-fold more potent (subnanomolar EC 50 values) than roflumilast at reducing IL-8, IL-29, IP-10, and RANTES mRNA and protein release, but had similar efficacies. In combination with the steroid fluticasone propionate (1 nmol/L), CHF6001 had additive effects, significantly reducing RV-induced cytokines when compared with steroid or CHF6001 alone. Combined low-dose steroid and low-dose CHF6001 had a similar efficacy as high-dose steroid or CHF6001 alone, indicating the combination had steroid and PDE4 inhibitor sparing effects. Overall results indicate that PDE4 inhibitors have anti-inflammatory activity against virus-induced inflammatory mediators and that CHF6001 is more potent than roflumilast.

Authors+Show Affiliations

Airway Disease Infection Section National Heart Lung Institute Imperial College London London United Kingdom; MRC and Asthma UK Centre for Allergic Mechanisms of Asthma London United Kingdom.Corporate Pre-clinical R&D Chiesi Farmaceutici S.p.A. Parma Italy.Corporate Pre-clinical R&D Chiesi Farmaceutici S.p.A. Parma Italy.Corporate Pre-clinical R&D Chiesi Farmaceutici S.p.A. Parma Italy.Airway Disease Infection Section National Heart Lung Institute Imperial College London London United Kingdom; MRC and Asthma UK Centre for Allergic Mechanisms of Asthma London United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26977295

Citation

Edwards, Michael R., et al. "Anti-inflammatory Effects of the Novel Inhaled Phosphodiesterase Type 4 Inhibitor CHF6001 On Virus-inducible Cytokines." Pharmacology Research & Perspectives, vol. 4, no. 1, 2016, pp. e00202.
Edwards MR, Facchinetti F, Civelli M, et al. Anti-inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus-inducible cytokines. Pharmacol Res Perspect. 2016;4(1):e00202.
Edwards, M. R., Facchinetti, F., Civelli, M., Villetti, G., & Johnston, S. L. (2016). Anti-inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus-inducible cytokines. Pharmacology Research & Perspectives, 4(1), pp. e00202. doi:10.1002/prp2.202.
Edwards MR, et al. Anti-inflammatory Effects of the Novel Inhaled Phosphodiesterase Type 4 Inhibitor CHF6001 On Virus-inducible Cytokines. Pharmacol Res Perspect. 2016;4(1):e00202. PubMed PMID: 26977295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus-inducible cytokines. AU - Edwards,Michael R, AU - Facchinetti,Fabrizio, AU - Civelli,Maurizio, AU - Villetti,Gino, AU - Johnston,Sebastian L, Y1 - 2016/01/15/ PY - 2015/08/03/received PY - 2015/10/30/revised PY - 2015/11/03/accepted PY - 2016/3/16/entrez PY - 2016/3/16/pubmed PY - 2016/3/16/medline KW - Asthma KW - chronic obstructive pulmonary disease KW - inflammation KW - phosphodiesterase inhibitor KW - rhinovirus SP - e00202 EP - e00202 JF - Pharmacology research & perspectives JO - Pharmacol Res Perspect VL - 4 IS - 1 N2 - Respiratory virus infections precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations, with most exacerbations due to rhinovirus infection. Both asthma and COPD exacerbations are not well controlled by steroid therapies, and there is a much research interest in finding improved therapies or combinations of therapies for controlling exacerbations. CHF6001 is a new, inhaled highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor. Using in vitro human bronchial epithelial cells (BEAS-2B), we investigated the potential anti-inflammatory effects of CHF6001 on rhinovirus (RV1B)-induced cytokines. Cytokine mRNA was measured by real-time PCR, while protein release was measured by ELISA. CHF6001 was used in a 7-point dose-response curve (1000-0.001 nmol/L) as a 1.5-h pretreatment prior to infection in comparison with roflumilast. Both roflumilast and CHF6001 reduced RV1B-induced IL-8, IL-29, IP-10, and RANTES mRNA and protein in a concentration-dependent manner. Generally, CHF6001 was 13- to 16-fold more potent (subnanomolar EC 50 values) than roflumilast at reducing IL-8, IL-29, IP-10, and RANTES mRNA and protein release, but had similar efficacies. In combination with the steroid fluticasone propionate (1 nmol/L), CHF6001 had additive effects, significantly reducing RV-induced cytokines when compared with steroid or CHF6001 alone. Combined low-dose steroid and low-dose CHF6001 had a similar efficacy as high-dose steroid or CHF6001 alone, indicating the combination had steroid and PDE4 inhibitor sparing effects. Overall results indicate that PDE4 inhibitors have anti-inflammatory activity against virus-induced inflammatory mediators and that CHF6001 is more potent than roflumilast. SN - 2052-1707 UR - https://www.unboundmedicine.com/medline/citation/26977295/Anti_inflammatory_effects_of_the_novel_inhaled_phosphodiesterase_type_4_inhibitor_CHF6001_on_virus_inducible_cytokines_ L2 - https://doi.org/10.1002/prp2.202 DB - PRIME DP - Unbound Medicine ER -