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

MCFARLIN, B. K., M. G. FLYNN, W. W. CAMPBELL, L. K. STEWART, and K. L. TIMMERMAN. TLR4 Is Lower in Resistance-Trained Older Women and Related to Inflammatory Cytokines. Med. Sci. Sports Exerc., Vol. 36, No. 11, pp. 1876-1883, 2004. 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 Q sets, 9 exercises, 10 repetitions at 80% of the I-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 (214), 6 h (6H), and 24 h (24H) after completion of exercise. Cell-surface expression of TLR4 (two-color immunofluorescent cytometry), LPS (25 mug-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 rnRNA 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(-1) for previous 24 months) resistance exercise training.