Production of inflammatory mediators by monocytes in patients with obstructive sleep apnea syndrome.
BACKGROUND
Obstructive sleep apnea syndrome (OSAS) is known to be a risk factor of cardiovascular events. However, the precise mechanism linking the two has not been fully elucidated.


OBJECTIVE
The aim of this study was to investigate the effect of hypoxic stress on the production of tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) by monocytes.


METHODS
Thirty-three OSAS patients and 13 healthy control subjects were enrolled. The OSAS patients were classified as mild-to-moderate (13) and severe (20). Venous blood samples were collected before and after sleep as well as after long-term nasal continuous positive airway pressure (CPAP) treatment for the purpose of isolation of monocytes. Peripheral blood monocytes were isolated using standard methods. Monocytes were cultured under lipopolysaccharide stimulation for 24 hours, and TNF-alpha, MCP-1, and MMP-9 in the culture supernatants were determined by ELISA.


RESULTS
In severe patients, the TNF-alpha production by monocytes was significantly elevated as compared to that before sleep (p<0.01). In all OSAS patients, the TNF-alpha production after sleep was significantly correlated with AHI (p<0.01), ODI (p<0.01) and % time in SpO(2)<90% (p<0.05), and inversely correlated with the lowest SpO(2) (p<0.01). The production of MCP-1 and MMP-9 by monocytes was significantly elevated compared to that before sleep in severe patients (p<0.05). The production of these mediators by monocytes was significantly decreased after long-term nasal CPAP treatment (p<0.05).


CONCLUSIONS
These results indicate that OSAS-induced hypoxic stress activates the production of inflammatory mediators by monocytes.
Tamaki
Shinji
S
Second Department of Internal Medicine, Nara Medical University, Nara.
Yamauchi
Motoo
M
Fukuoka
Atsuhiko
A
Makinodan
Kiyoshi
K
Koyama
Noriko
N
Tomoda
Koichi
K
Yoshikawa
Masanori
M
Kimura
Hiroshi
H
D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000096:biosynthesis; D045422:Continuous Positive Airway Pressure; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D020181:Sleep Apnea, Obstructive / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D013312:Stress, Physiological; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9