Tumor necrosis factor-alpha expression in uvular tissues differs between snorers and apneic patients.
BACKGROUND
Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-alpha has been shown to affect diaphragm contractility in mice and rabbit in vivo.


OBJECTIVE
To assess total and compartmental TNF-alpha expression in uvular tissues of apneic and nonapneic patients.


METHODS
Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-alpha expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections.


RESULTS
TNF-alpha was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean +/- SEM] snorers, 100.5 +/- 3.0%; OSA 1 group, 127.1 +/- 6.9%; OSA 2 group, 140.7 +/- 11.0%; p = 0.01). In the muscular area, TNF-alpha levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 +/- 3%; OSA 1 group, 107.4 +/- 0.7%; OSA 2 group, 124.1 +/- 4.2%; p = 0.007). In the muscular area, TNF-alpha was correlated with BMI, but no relationship was found with the apnea-hypopnea index.


CONCLUSIONS
We conclude that MU is the major TNF-alpha source in uvular tissue and that TNF-alpha is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.
Loubaki
Lionel
L
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Québec, QC, Canada.
Jacques
Eric
E
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Québec, QC, Canada.
Semlali
Abdelhabib
A
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Québec, QC, Canada.
Biardel
Sabrina
S
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Québec, QC, Canada.
Chakir
Jamila
J
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Québec, QC, Canada. Electronic address: jamila.chakir@med.ulaval.ca.
Sériès
Frédéric
F
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Québec, QC, Canada.
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000378:metabolism*; D012913:Snoring / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014609:Uvula / Q000378:metabolism*
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha