TLR4 is lower in resistance-trained older women and related to inflammatory cytokines

Med Sci Sports Exerc. 2004 Nov;36(11):1876-83. doi: 10.1249/01.mss.0000145465.71269.10.


Introduction/purpose: Regular exercise may offset age-associated increases in inflammatory cytokines and reduce the risk of developing diseases with an inflammatory etiology by exerting "anti-inflammatory" effects. Toll-like receptor 4 (TLR4) signaling stimulates inflammatory cytokine production, and may explain the "anti-inflammatory" effect attributed to regular exercise. Therefore, the purpose of the present study was to compare the effect of acute (3 sets, 9 exercises, 10 repetitions at 80% of the 1-repetition maximum) and chronic resistance exercise on TLR4 and inflammatory cytokines.

Methods: Venous blood samples were collected from trained (TR, N = 10) and untrained (UT, N = 10) older (65-80 yr) postmenopausal women: before (PRE), immediately post (POST), and 2 h (2H), 6 h (6H), and 24 h (24H) after completion of exercise. Cell-surface expression of TLR4 (two-color immunofluorescent cytometry), LPS (25 microg x mL(-1))-stimulated cytokine production (ELISA), plasma cytokines (ELISA), and mRNA expression of TLR4 and cytokines (RT-PCR) were determined for each sample.

Results: TR had 124% less cell-surface TLR4 expression than UT (P < 0.05). A significant time effect was found for LPS-stimulated IL-6, IL-1beta, and TNF-alpha, where 6H was significantly greater than all other samples. No significant effects were found for plasma (IL-6 and TNF-alpha) or mRNA expression (IL-6, TNF-alpha, and IL-1beta) of inflammatory cytokines. When subjects were grouped according to cell-surface TLR4 expression (HI and LO), LPS-stimulated TNF-alpha (302%), IL-1beta (209%), and IL-6 (167%) production was greater for HI than LO (P < 0.05).

Conclusion: Regularly exercising older women expressed less cell-surface TLR4 but did not have lower plasma levels or produce less LPS-stimulated inflammatory cytokines at rest or in response to a single bout of resistance exercise. TLR4 changes may explain the "anti-inflammatory" effect that has recently been attributed to chronic (2x wk for previous 24 months) resistance exercise training.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology
  • Aged / physiology*
  • Blood Cell Count
  • Cross-Sectional Studies
  • Cytokines / metabolism*
  • Diet
  • Exercise / physiology*
  • Female
  • Humans
  • Inflammation / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Motor Activity / physiology*
  • Postmenopause
  • Receptors, Cell Surface / metabolism*
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Weight Lifting / physiology*


  • Cytokines
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors