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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.

Abstract：

: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 (%FEV1 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.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Douaoui S,Djidjik R,Boubakeur M,Ghernaout M,Touil-Boukoffa C,Oumouna M,Derrar F,Amrani Y

doi

10.1016/j.imbio.2020.151950

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

151950

issue

3

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(20)30126-1

journal_volume

225

pub_type

杂志文章

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