Changes of circadian rhythms of melatonin and cytokines in obstructive sleep apnea syndrome

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10670535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TOJO Naoko Tokyo Medical and Dental University Faculty of Medicine the lecturer, 医学部, 助手 (90227554)
• Project Period (FY): 1998 – 1999
• Keywords: obstructive sleep apnea syndrome (OSAS) / melatonin / cytokines / tumor necrosis factor (TNF-alpha)

Research Abstract

BACKGROUND : Sleep is regulated by neural and humoral factors. Melatonin and several cytokines have been shown to be somnogenic (e.g. interleukin-1 [IL-1], tumor neurosis factor-alpha [TNF-alpha]). Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent apneas caused by occlusion of the upper airway during sleep, and patients with OSAS exhibit dramatic fragmentation of sleep and excessive daytime somnolence. Nasal continuous positive airway pressure ventilation (nasal CPAP) can effectively treat these patients.
Seeking the interaction between abnormalities of somnogenic humoral factors and excessive daytime somnolence of patients with OSAS, we investigated whether circadian rhythms of melatonin and several cytokines secretion were altered in patients with OSAS.
METHODS : Eight subjects were enrolled in the study. All of them gave informed consent. All patients were studies with all-night polysomnography, and blood samples were collected every 4 h from 6:00 A.M. to 10:00 P.M . and at 2h intervals on the following night using catheters in a forearm vein, and melatonin plasma levels and cytokines secretion (IL-1-beta, IL-10, TNF-alpha) were determined. Three of the 8 OSAS patients were reexamined after 3 to 6 mo of therapy with nasal CPAP. Using Epworth Sleepiness Scale (ESS), we evaluated excessive daytime somnolence in patients with OSAS.
RESULTS : The circadian rhythm of melatonin and TNF-alpha secretion was significantly disturbed in three of 8 OSAS patients : nocturnal physiologic peaks in these substances had almost disappeared and an additional daytime peak had developed. These three patients exhibited higher apnea index. lower SpO2, and higher ESS. Nasal CPAP therapy almost normalized melatonin and TNF-alpha rhythms. Correrations between circadian variations in IL-1, IL-10 and ESS were not shown.
CONCLUSION : These results suggest that abnormalities of melatonin and TNF-alpha rhythms may play a key role in the expression of the daytime somnolence in patients with severe OSAS.