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  Vol. 166 No. 16, September 18, 2006 TABLE OF CONTENTS
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Soluble Interleukin 6 Receptor

A Novel Marker of Moderate to Severe Sleep-Related Breathing Disorder

Reena Mehra, MD, MS; Amy Storfer-Isser, MS; H. Lester Kirchner, PhD; Nathan Johnson; Nancy Jenny, PhD; Russell P. Tracy, PhD; Susan Redline, MD, MPH

Arch Intern Med. 2006;166:1725-1731.

Background  Given the previously described association between sleep-related breathing disorder (SRBD) and markers of inflammation, we assessed the relationship of SRBD with levels of both interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R), a marker with more expansive physiologic effects than IL-6. The objectives were to explore the relationship between moderate to severe sleep apnea with IL-6 and sIL-6R levels and to examine morning and evening variability for each cytokine.

Methods  A total of 385 adult participants (≥18 years of age) in the Cleveland Family Study, Cleveland, Ohio, underwent sleep studies and determination of IL-6 and sIL-6R levels in samples obtained in the evening and morning of polysomnography. Moderate to severe SRBD was defined as a respiratory disturbance index greater than or equal to 30.

Results  The subjects were aged 44.9 ± 16.7 (mean ± SD) years, 44% were male, and 48% were African American, with a body mass index (weight in kilograms divided by the height in meters squared) of 32.5 ± 8.1 (mean ± SD). Linear regression analysis showed that after adjustment for subject characteristics, waist circumference, and comorbidities, SRBD was not significantly associated with morning IL-6 levels. In contrast, linear regression analyses showed that, compared with the participants without SRBD, those with SRBD had significantly higher morning sIL-6R levels (mean ± SD, 4.60 ± 1.42 ng/mL [P = .001]), even after adjustment for subject characteristics, waist circumference, and comorbidities, which persisted after adjustment of evening sIL-6R levels.

Conclusions  Morning sIL-6R levels demonstrated stronger associations with moderate to severe SRBD than morning IL-6 levels. Associations with SRBD and morning sIL-6R levels persisted even after adjustment for waist circumference, cardiovascular disease, and evening sIL-6R levels, suggesting the potential utility of sIL-6R as a marker for measuring overnight SRBD stresses. Further investigation of this biomarker may provide insight into SRBD-related inflammation.


Author Affiliations: Departments of Medicine (Drs Mehra and Redline) and Pediatrics (Drs Mehra, Kirchner, and Redline, Ms Storfer-Isser, and Mr Johnson), Case School of Medicine, Cleveland, Ohio; and Departments of Biochemistry and Pathology, University of Vermont, Burlington (Drs Jenny and Tracy).



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