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GTS-21, an α7nAChR agonist, suppressed the production of key inflammatory mediators by PBMCs that are elevated in COPD patients and associated with impaired lung function

journal contribution
posted on 30.04.2020, 09:22 by Sana DOUAOUI, Reda DJIDJIK, Mokhtar BOUBAKEUR, Merzak GHERNAOUT, Chafia TOUIL-BOUKOFFA, Mustapha OUMOUNA, Fawzi DERRAR, Yassine Amrani

Chronic obstructive pulmonary disease (COPD) is a lung inflammatory disease characterized by progressive airflow limitation, chronic respiratory symptoms and frequent exacerbations. There is an unmet need to identify novel therapeutic alternatives beside bronchodilators that prevent disease progression. Levels of both Nitric Oxide (NO) and IL-6 were significantly increased in the plasma of patients in the exacerbation phase (ECOPD, n=13) when compared to patients in the stable phase (SCOPD, n=38). Levels of both NO and IL-6 were also found to inversely correlate with impaired lung function (þV1 predicted). In addition, there was a strong positive correlation between levels of IL-6 and NO found in the plasma of patients and those spontaneously produced by their peripheral blood mononuclear cells (PBMCs), identifying these cells as a major source of these key inflammatory mediators in COPD. GTS-21, an agonist for the alpha 7 nicotinic receptors (α7nAChR), was found to exert immune-modulatory actions in PBMCs of COPD patients by suppressing the production of IL-6 and NO. This study provides the first evidence supporting the therapeutic potential of α7nAChR agonists in COPD due to their ability to suppress the production of key inflammatory markers associated with disease severity.

Funding

This study was supported by the Ministry of Higher Education and Scientific Research (Algeria) and by the National Institute for Health Research Leicester Biomedical Research Centre Respiratory.

History

Citation

Immunobiology, 2020, In Press

Version

AM (Accepted Manuscript)

Published in

Immunobiology

Publisher

Elsevier

issn

0171-2985

Acceptance date

20/04/2020

Copyright date

2020

Publisher version

TBA

Language

en

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