Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in healthy volunteers

Brain Behav Immun. 2004 Jul;18(4):361-7. doi: 10.1016/j.bbi.2003.12.009.


There is very little published information on the diurnal variation of cytokines and their receptors, in healthy individuals during normal sleep-wake patterns or during sustained wakefulness. The aim of the current investigation was to characterize concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) and interleukin-2 receptor (sIL-2R) during normal sleep and wakefulness, as well as during a 24 h vigil. Plasma levels of the sTNF-R p55, sTNF-R p75, and sIL-2R did not differ significantly between nocturnal sleep and nocturnal wakefulness. Rhythmic analysis (2-h intervals) revealed significant diurnal variations for both sTNF-R p55 and sTNF-R p75, but not levels of sIL-2R. Diurnal variations of both sTNF-Rs were characterized by a single cosine curve with an average peak near 06:00 h in the morning. This peak occurred well before that of cortisol, and fluctuated inversely with the diurnal rhythm of temperature. These diurnal variations in sTNF-Rs levels are consistent with the hypothesis that the TNF system plays a role in normal diurnal temperature regulation.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Antigens, CD / blood*
  • Circadian Rhythm / immunology*
  • Circadian Rhythm / physiology
  • Humans
  • Hydrocortisone / blood
  • Male
  • Receptors, Interleukin-2 / blood*
  • Receptors, Tumor Necrosis Factor / blood*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Reference Values
  • Sleep / physiology
  • Sleep Deprivation / blood*
  • Wakefulness / physiology


  • Antigens, CD
  • Receptors, Interleukin-2
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Hydrocortisone