Increased upper airway cytokines and oxidative stress in severe obstructive sleep apnoea

Abstract

Inflammation may contribute to upper airway pathophysiology in obstructive sleep apnoea (OSA). Our objective was to compare upper airway pro-inflammatory cytokine expression, oxidative stress and connective tissue deposition in severe (n525) versus mild (n517) OSA patients.Upper airway surgical specimens were separated by predominance of either mucosal or muscle tissue. Expression levels of interleukin (IL)-1a, IL-6, interferon-c, RANTES (regulated on activation, normal T-cell expressed and secreted), transforming growth factor (TGF)-b and L-selectin were measured by ribonuclease protection assay. Oxidative stress was assessed via protein carbonyl group detection by immunoblotting. Histochemistry was employed for immunolocalisation of selected cytokines and connective tissue morphometry.In the severe OSA group, expression of IL-1a, IL-6 and TGF-b was significantly higher in mucosa-predominant tissues, whereas in muscle-predominant specimens, RANTES expression was greater in severe OSA. Increased protein carbonylation was observed in severe OSA within both mucosal and muscle compartments. Immunohistochemistry localised TGF-b to submucosal and perimuscular inflammatory cells, while IL-6 was primarily localised to myocytes. Consistent with the pro-fibrotic cytokine profile observed in mucosa-predominant tissue, morphometric analysis revealed greater submucosal and perimuscular connective tissue in severe OSA subjects.There is increased pro-inflammatory and pro-fibrotic cytokine expression, oxidative stress, and connective tissue deposition in upper airway tissues from severe versus mild OSA patients.

Asthma-related comorbidities

“…First, it is associated with an upper airway inflammatory process that has the potential to influence lower airways. In this regard, significant systemic and upper airway inflammation has been reported with OSA [106,107], and Devouassoux et al reported bronchial neutrophilia and a high IL-8 concentration in patients with untreated OSA compared with controls [108].…”

Effects of Inhaled Fluticasone on Upper Airway during Sleep and Wakefulness in Asthma: A Pilot Study

“…Inflammation in the pharyngeal UAW has been linked to profibrotic cytokines and collagen deposition. 45 Collectively, these observations suggest that sustained inflammation leads to UAW remodeling which could adversely affect tissue compliance and/or its mechanical coupling, translating into impaired ability to sustain increased demands. 45 How ICS impact the structure and function of skeletal muscles, such as those of the pharyngeal UAW, remains to be studied.…”

5-HTR2A and IL-6 polymorphisms and obstructive sleep apnea-hypopnea syndrome

“…Therefore, inflammation may contribute to upper airway pathophysiology and OSAHS is usually associated with increasing levels of inflammatory cytokines (10)(11)(12). At present, a previous study revealed the correlation between the polymorphism located in the promoter region of the inflammatory cytokine genes and OSAHS (13).…”

“…IL-6 is a circulating cytokine, known to be secreted from a number of different cells, including activated macrophages and lymphocytes. Evidence has demonstrated that the plasma levels of pro-inflammatory cytokines, such as IL-6, are observed to be elevated in OSAHS patients, are associated with the severity of disease (12) and are significantly reduced following continuous positive airway pressure therapy (14). It appears reasonable to hypothesize that abnormalities in the IL-6 gene could be relevant to the etiology of OSAHS.…”