Elsevier

Cytokine

Volume 28, Issue 2, 21 October 2004, Pages 87-91
Cytokine

The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome

https://doi.org/10.1016/j.cyto.2004.07.003Get rights and content

Abstract

Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) may have a direct effect on glucose and lipid metabolism. On the other hand, it is known that IL-6 and TNF-α are important pro-inflammatory cytokines in the pathogenesis of atherosclerosis. The goal of present study was to test whether sleep apnea contributes to the previously reported increases of IL-6 and TNF-α independent of obesity. Forty-three obese (body mass index, BMI > 27 kg/m2) men with newly diagnosed obstructive sleep apnea syndrome (OSAS) (apnea–hypopnea index, AHI  5) and age- and BMI-matched 22 obese nonapneic male controls (AHI < 5) were enrolled in this study. To confirm the diagnosis, all patients underwent standard polysomnography in the sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting. Serum IL-6 and TNF-α levels were found significantly higher in OSAS patients than in controls (p = 0.002, p = 0.03). Serum IL-6 and TNF-α levels were significantly correlated with AHI in OSAS patients (r = 0.03, p = 0.046 and r = 0.36, p = 0.016). There was no significant correlation between serum IL-6, TNF-α levels and AHI in controls. Serum IL-6 and TNF-α levels were not correlated with BMI both in OSAS patients and controls. In conclusion, circulating IL-6 and TNF-α levels in patients with OSAS, as independent of BMI are significantly higher than levels in controls and there is a positive relationship between previously mentioned cytokines' levels and the severity of OSAS. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating IL-6 and TNF-α levels.

Introduction

Obstructive sleep apnea syndrome (OSAS), characterized by repeated episodes of upper airways obstruction during sleep leading to significant hypoxemia, is a very prevalent disorder particularly among middle-aged obese men, although its existence in women is increasingly recognized. Epidemiological studies estimate that 2–5% of the population meets the minimal diagnostic criteria, and two community-based studies have found that about 2% of women and 4% of men were affected by OSAS [1].

Serum pro-inflammatory cytokines follow a circadian rhythm, with peaks between 01:00 and 02:00 h, when slow wave sleep usually occurs, suggesting a potential physiological role of these cytokines in normal sleep [2]. In 1997, Vgontzas et al. reported that the pro-inflammatory cytokines such as IL-6 and TNF-α were elevated in patients with disorders of EDS and these elevations are significant in OSAS. They proposed that these cytokines are the mediators of daytime sleepiness [3], [4]. Beginning from this date, the association between inflammation and OSAS was more attracted.

On the other hand, pro-inflammatory cytokines have a direct effect on glucose and lipid metabolism [5] and it is demonstrated a positive association between obesity and serum pro-inflammatory cytokines' levels in humans [6]. The aim of present study was to test whether increases in IL-6 and TNF-α were independent of obesity in patients with OSAS. For this propose, we examined the serum IL-6 and TNF-α levels in obese patients with OSAS and obese control subjects.

Section snippets

Patients

Forty-three obese (BMI > 27 kg/m2) men with newly diagnosed OSAS and age- and BMI-matched 22 obese nonapneic male controls were enrolled in this study. Subjects with obesity were recruited from the outpatient clinic for the examination of sleep apnea. The Epworth Sleepiness Scale (ESS) was used to investigate changes in subjective daytime sleepiness. BMI was calculated as weight in kilograms divided by the square of the height measured by a scale. Neck circumference, taking at the level of the

Results

Serum IL-6 and TNF-α levels were found significantly higher in OSAS patients than in controls (p = 0.002 and p = 0.03, respectively). Mean of IL-6 was 6.12 ± 4.44 in controls, and 11.71 ± 9.8 in OSAS patients. Mean of TNF-α was 3.29 ± 2.13 in controls and 4.6 ± 3.39 in OSAS patients (Table 2 and Fig. 1). Serum IL-6 levels were significantly and positively correlated with AHI and neck circumference in OSAS patients (r = 0.33, p = 0.03 and r = 0.03, p = 0.046, respectively) (Fig. 2).

TNF-α levels were significantly

Discussion

In patients with OSAS, cyclical alterations of arterial oxygen saturation are observed with oxygen desaturation developing in response to apnea followed by the resumption of oxygen saturation during hyperventilation. This phenomenon has been referred to as hypoxia/reoxygenation and might alter the oxidative balance through the induction of excess oxygen free radicals quite like in the sequelae of ischemia/reperfusion injury. Hypoxia functions as a danger signal for the immune system by inducing

References (20)

  • G.E. Carpagnano et al.

    Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients

    Chest

    (2002)
  • H. Moldofsky et al.

    Sleep Med Rev

    (1999)
  • A.G. Bassiri et al.

    Clinical features and evaluation of obstructive sleep apnea–hypopnea syndrome

  • J. Bauer et al.

    Interleukin-6 serum levels in healthy persons correspond to the sleep–wake cycle

    Clin Invest

    (1994)
  • A.N. Vgontzas et al.

    Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity

    J Clin Endocrinol Metab

    (1997)
  • A.N. Vgontzas et al.

    Metabolic disturbances in obesity versus sleep apnoea; the importance of visceral obesity and insulin resistance

    J Intern Med

    (2003)
  • L. Roytblat et al.

    Raised interleukin-6 levels in obese patients

    Obes Res

    (2000)
  • P. Pasulka et al.

    Obesity and erythrocyte sedimentation rates

    Ann Intern Med

    (1985)
  • A. Rechtschaffen et al.

    A manual of standardized terminology, techniques, and scoring system for sleep stages in human subjects

    (1968)
  • EEG arousals, scoring rules and examples: a preliminary report from the sleep disorders atlas task force of the ASDA

    Sleep

    (1992)
There are more references available in the full text version of this article.

Cited by (0)

View full text