PT  - JOURNAL ARTICLE
AU  - Ailbhe King
AU  - Susan Fitzpatrick
AU  - Cliona O'Donnell
AU  - Silke Ryan
TI  - The GLP-1 receptor agonist Liraglutide attenuates intermittent hypoxia-induced pro-inflammatory macrophage polarization in primary macrophages
AID  - 10.1183/13993003.congress-2021.OA3018
DP  - 2021 Sep 05
TA  - European Respiratory Journal
PG  - OA3018
VI  - 58
IP  - suppl 65
4099  - http://erj.ersjournals.com/content/58/suppl_65/OA3018.short
4100  - http://erj.ersjournals.com/content/58/suppl_65/OA3018.full
SO  - Eur Respir J2021 Sep 05; 58
AB  - Background: Intermittent hypoxia (IH)-induced pro-inflammatory M1-macrophage polarization likely plays a key role in the pathogenesis of metabolic perturbations in obstructive sleep apnoea (OSA). We have recently shown using primary macrophages that this response is mediated through the TLR4/NFκB pathway1 and thus, this pathway may represent a potential therapeutic target. Recent evidence suggested attenuation of pro-inflammatory response in macrophages by the glucagon-like peptide-1 receptor (GLP-1R) agonist, Liraglutide. Here, we tested the hypothesis that Liraglutide protects against IH-induced responses using our state-of-the-art in-vitro model of IH.Methods: Bone marrow-derived macrophages isolated from C56BL/6 male mice were exposed to IH or intermittent normoxia as previously described1 in the presence or absence of 250nM Liraglutide. RNA was extracted and analysed via RT-qPCR for expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and iNOS.Results: As expected, IH resulted in increased mRNA expression of the potent pro-inflammatory macrophage markers iNOS, IL-1β and IL-6, in comparison to normoxic controls. Liraglutide significantly attenuated the IH-mediated increase in IL-1β (0.5±0.42 fold over control, p=0.031) and iNOS (0.14±0.18 fold over control, p=0.001) and there was a trend towards reduced expression in IL-6.Conclusion: Liraglutide attenuates IH-induced pro-inflammatory responses in primary macrophages. Further experiments in-vitro and in-vivo will determine the role of this intervention in metabolic diseases in OSA.1Fitzpatrick SF et al, J Sleep Res: e13202FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA3018.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).