Macrophage Migratory Inhibitory Factor May Contribute to the Production of Nitric Oxide in Obstructive Sleep Apnea.

Abstract

In obstructive sleep apnea (OSA), repeated airway obstruction alters mucosal inflammation, which increases exhaled nitric oxide (NO) production in the nasal cavity. However, the underlying mechanism remains unclear. Accordingly, we aimed to examine the mechanism underlying NO production in patients with OSA. We included eight patients with moderate-to-severe OSA who underwent continuous positive airway pressure (CPAP) therapy. Nasal cavity NO levels were measured before and after CPAP; additionally, the levels of inflammatory cytokines in the supernatants of nasal mucosal samples and mRNA expression of inflammation-related molecules in epithelial cells were analysed. Additionally, we examined changes in inflammation-related molecules following stimulation of airway epithelial cells with the aforementioned supernatants and after CPAP treatment. Consistent with previous reports, nasal cavity NO levels improved after the introduction of CPAP therapy. There was a significant post-treatment decrease in the levels of macrophage migration inhibitory factors (MIF) in the nasal mucosal cavity. Additionally, there was a post-treatment increase in mRNA expression of SIRT1, as well as decreased mRNA expression of HIF-1α and inducible nitric oxide synthase (iNOS), in nasal mucosal epithelial cells. Similar results were obtained in airway epithelial cells stimulated with supernatants from nasal mucosal samples. Furthermore, airway epithelial cells stimulated with recombinant MIF showed decreased SIRT1 expression, as well as increased HIF-1α and iNOS expression. This study describes local inflammatory changes in the nasal mucosa of patients with OSA, suggesting that MIF is involved in NO production. Appropriate therapeutic intervention with CPAP can effectively control this inflammation.