Reciprocal Relationship Between Sleep Macrostructure and Evening and Morning Cellular Inflammation in Rheumatoid Arthritis

Psychosom Med. 2017 Jan;79(1):24-33. doi: 10.1097/PSY.0000000000000363.

Abstract

Objective: This study examined the reciprocal associations between sleep macrostructure and levels of cellular inflammation in rheumatoid arthritis (RA) patients and controls.

Methods: RA patients (n = 24) and matched controls (n = 48) underwent all-night polysomnography, along with assessment of spontaneous- and Toll-like receptor-4-stimulated monocytic production of tumor necrosis factor α (TNF) and interleukin (IL)-6 at 11:00 PM and 8:00 AM.

Results: As compared with controls, RA patients showed lower levels of sleep efficiency (mean [standard deviation], 88.1 [6.1] versus 83.8 [7.0]), a higher percentage stage 3 sleep (9.3 [6.4] versus 13.1 [6.9]), and higher levels of percentage of monocytes either spontaneously expressing TNF at 11:00 PM (log transformed, 1.07 [0.28] versus 1.22 [0.17]), and higher Toll-like receptor-4-stimulated production of IL6 at 8:00 AM (log transformed, 3.45 [0.80] versus 3.83 [0.39]). Higher levels of stimulated production of TNF at 11:00 PM were associated with higher sleep efficiency (0.74). In turn, sleep efficiency had a countervailing relationship on TNF production at 8:00 AM (-0.64). Higher levels of spontaneous and stimulated production of IL6 at 11:00 PM were associated with more stage 3 (0.39), stage 4 (0.43), and slow-wave sleep (0.49), with evidence that stage 4 had a countervailing relationship on IL6 production at 8:00 AM (-0.60).

Conclusions: RA patients show evidence of sleep fragmentation, greater sleep depth, and higher levels of cellular inflammation. Sleep maintenance and sleep depth show countervailing relationships with evening and morning levels of monocytic production of TNF and IL-6, respectively, which support the hypothesis of a feedback loop between sleep maintenance, slow-wave sleep, and cellular inflammation that is cytokine specific.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology*
  • Female
  • Humans
  • Inflammation / immunology*
  • Interleukin-6 / metabolism*
  • Male
  • Middle Aged
  • Periodicity
  • Polysomnography
  • Sleep Stages / immunology*
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • IL6 protein, human
  • Interleukin-6
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha