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TLR4 Is Lower in Resistance-Trained Older Women and Related to Inflammatory Cytokines


Medicine & Science in Sports & Exercise: November 2004 - Volume 36 - Issue 11 - p 1876-1883
doi: 10.1249/01.MSS.0000145465.71269.10
Basic Sciences: Original Investigations

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 μg·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-1β, and TNF-α, where 6H was significantly greater than all other samples. No significant effects were found for plasma (IL-6 and TNF-α) or mRNA expression (IL-6, TNF-α, and IL-1β) of inflammatory cytokines. When subjects were grouped according to cell-surface TLR4 expression (HI and LO), LPS-stimulated TNF-α (302%), IL-1β (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 (2× wk−1 for previous 24 months) resistance exercise training.

1Wastl Human Performance Laboratory, Department of Health and Kinesiology, 2Department of Foods and Nutrition, and 3Department of Health and Human Performance, University of Houston, Houston, TX

Address for correspondence: Brian K. McFarlin, Ph.D., University of Houston, Department of Health and Human Performance, Houston, TX 77204-6015; E-mail:

Submitted for publication January 2004.

Accepted for publication June 2004.

The authors would also like to thank Anna Thalacker for analyzing the dietary records.

This project was funded in part by a grant from the American College of Sports Medicine.

©2004The American College of Sports Medicine