Dynamics in Pro-Inflammatory Cytokines in Response to Hypoglossal Nerve Stimulation in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is associated with chronic low-grade systemic inflammation. In cases of continuous positive airway pressure (PAP) failure, hypoglossal nerve stimulation (HNS) is a treatment option for OSA but its impact on systemic inflammation to date is unknown. Herein, we investigated changes in cytokines and endothelial markers before and after HNS.

Eighteen adults with moderate or severe OSA underwent fasting blood sample collection before and 6-8 months after HNS implantation. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang2), C-reactive protein (CRP), and E-selectin were measured using ELISA. Clinical metrics, including apnea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS), were assessed.

HNS significantly reduced AHI (from 25.9 ± 13.4 to 14.2 ± 10.5) and ESS scores (from 12.6 ± 5.0 to 7.1 ± 4.0). There were significant decreases in VEGF (p = 0.033) and TNF-α (p = 0.0013) with HNS. CRP levels were elevated among OSA patients when compared with healthy donors and did not change after HNS. IL-6 levels did not change with HNS, but were low in both healthy and OSA patients. No significant overall changes were observed in Ang2 or E-selectin. Obese participants exhibited higher baseline inflammatory profiles compared with non-obese participants.

In this small cohort, HNS improved OSA severity and was associated with decreases in VEGF and TNF-α while other inflammatory markers were unchanged. Larger, long-term studies are needed to understand the potential of HNS to confer cardiometabolic benefits through reduction of systemic inflammation in OSA.