Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men

Eur Cytokine Netw. Jul-Sep 2014;25(3):52-7. doi: 10.1684/ecn.2014.0356.


Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (P<0.01 respectively), as well as TLR-4 (P<0.05), while IL-6 mRNA levels remained unchanged. Circulating concentrations of free IGF-I were decreased at D4 (P<0.001). One night of recovery was sufficient to restore basal expression levels for TNF-α, sTNF-R1, TLR-4 and circulating IGF-I. Changes in TLR-4 mRNA levels during the protocol correlated positively with those of TNF-α and sTNF-R1 (r=0.393 and r=0.490 respectively), and negatively with circulating free IGF-I (r=-0.494). In conclusion, 25 h of sleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.

Keywords: IGF-1 system; Toll-like receptor 4; healthy men; proinflammatory cytokines; sleep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Gene Expression / genetics
  • Humans
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Interleukin-6 / metabolism
  • Male
  • RNA, Messenger / genetics
  • Sleep Deprivation / genetics*
  • Sleep Deprivation / metabolism*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-6
  • RNA, Messenger
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Insulin-Like Growth Factor I