Cholinergic Markers and Cytokines in OSA Patients.

Marcella Reale,Biancamaria Guarnieri,Gianluigi Cerroni,Chiara D’Angelo,Lucia Velluto,Michele Marchioni,Erica Costantini,Marta Di Nicola

doi:10.3390/ijms21093264

Marcella Reale, Biancamaria Guarnieri + Show 6 more

Open Access

https://doi.org/10.3390/ijms21093264

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Abstract

The role of inflammation and dysfunction of the cholinergic system in obstructive sleep apnea (OSA) has not exhaustively clarified. Thus, in this study, we explore the non-neuronal cholinergic system and the balance of T helper (Th) 17- and T regulatory (Treg)-related cytokines in OSA patients. The study includes 33 subjects with obstructive sleep apnea and 10 healthy controls (HC). The expression levels of cholinergic system component, RAR-related orphan receptor (RORc), transcription factor forkhead box protein 3 (Foxp3) and cytokines were evaluated. Th17- and Treg-related cytokines, choline levels and acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activity were quantified in OSA and control subjects. AChE and nicotinic receptor α 7 subunit (α7nAChR) gene expression and serum levels of choline, AChE and BuChE were lower in OSA patients than in the HC group. Compared with the HC group, OSA patients exhibited an increased expression, secretion and serum levels of pro-inflammatory cytokines, a reduced expression, secretion and serum levels of transforming growth factor (TGF)β and reduced Foxp3 mRNA levels. The Th17/Treg-related cytokine ratio was higher in the OSA group. Our results confirm and reinforce the hypothesis that OSA may be considered a systemic inflammatory disease, and that an imbalance of non-neuronal cholinergic and pro/anti-inflammatory cytokines may contribute to development and progression of comorbidities in OSA subjects. The evaluation of Th17/Treg-related cytokine may provide an additional explanation for OSA pathogenesis and clinical features, opening new directions for the OSA management.

Highlights

obstructive sleep apnea (OSA) is a major primary sleep disorder characterized by repetitive nocturnal complete or partial, collapses of the upper airway during sleep accompanied by oxyhemoglobin desaturation and/or electroencephalography (EEG) and vegetative arousals
Our aim is to investigate, in OSA patients, the non-neuronal cholinergic system and the Th17- and T regulatory (Treg)-related cytokines and if nicotinic receptor α7 subunit is involved in Th17/Treg polarization and the synthesis of proinflammatory cytokines
The demographic characteristics are not different between gender in our OSA patients, the women were all in post-menopausal age (i.e., ≥ 54 years) (Table 1)

Summary

Introduction

OSA is a major primary sleep disorder characterized by repetitive nocturnal complete (apnea) or partial (hypopnea), collapses of the upper airway during sleep accompanied by oxyhemoglobin desaturation and/or electroencephalography (EEG) and vegetative arousals. Nocturnal OSA symptoms include sleep fragmentation, diminished amounts of slow wave and rapid eye movement (REM) sleep, nocturia and insomnia. Depressive symptoms, cognitive alterations, fatigue and, in particular excessive daytime sleepiness (EDS), with different patterns between men and women [1,2,3]. EDS is not always present in OSA patients, and it does not invariably correlate with the severity of the disease, showing inter-individual differences with different responses to ventilatory treatments, albeit these aspects need to be better elucidated [4]. Clinical studies of OSA and inflammation have yielded conflicting results and suggested that there are patient-specific or OSA-specific factors that predict inflammation, but which have not yet been fully identified

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