Physical Activity Status, but not Age, Influences Inflammatory Cytokine Production and Toll-like Receptor 4

Abstract

INTRODUCTION/PURPOSE. Chronic inflammation has been implicated in the development of cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis. Regular physical activity has been purported to possess “anti-inflammatory” properties which may lower chronic inflammation. Recently, we hypothesized that toll-like receptor 4 (TLR4) plays a role in activity-induced modulation of inflammation. Therefore, the purpose of this study was to determine the association between age, physical activity status, biomarkers of inflammation, and TLR4. METHODS: Men and women were recruited and assigned to one of four groups: young (18–30 y), inactive (YI, n=21); young, active (YA, n=23); old (65–75 y), inactive (OI, n=21); or old, active (OA, n=23). To assess physical activity status, subjects completed a Paffenbarger physical activity questionnaire (daily physical activity) and a modified Balke submaximal treadmill test (estimated VO2max). After screening, subjects were given a standard mixed diet to consume 24-h prior to arriving at the lab. Subjects arrived at the lab between 0600 and 0800 following an overnight fast (8-h). Following 30-min of seated rest in a quiet room, venous blood samples were collected. Lipopolysaccharide (LPS)-stimulated inflammatory cytokine production was determined from whole blood cultures and subsequent ELISA. TLR4 expression was determined by two-color flow cytometry. Data were analyzed using a 2 (young & old) × 2 (active & inactive) factor ANOVA. RESULTS: Estimated VO2max (P <0.05) and daily physical activity (P<0.05) were significantly greater in YA (47.9± 8.7 ml/kg/min, 2.7± 0.7 h/wk) and OA (39. 1± 8.0 ml/ kg/min, 2.7± 0.8 h/wk) than YI (31.9± 7.3 ml/kg/min, 0.4± 0.5 h/wk) and OI (25.0± 5.8 ml/kg/min, 0.5± 0.6 h/wk). LPS-stimulated IL-6 (24%, P =0.002), IL-1β (22%, P =0.023), and TNF-α (21%, P =0.016) productions was greater in inactive (YI & OI) compared to active subjects (YA & OA). TLR4 expression (MFI) was 32% greater in inactive compared to active (P =0.002). Quantity of daily physical activity was negatively correlated with IL-6 production, IL-1 β production, and TLR4 expression (P<0.05). CONCLUSIONS: The findings of the present study support previous reports which infer acute exercise or a physically active lifestyle may possess “anti-inflammatory” properties.