Mechanisms for the anti -inflammatory effects of exercise training

Kyle Lee Timmerman, Purdue University

Abstract

The purpose of this research was to examine the influence of physical activity and 12 weeks of exercise training on monocyte phenotype, monocyte TLR4 expression, CD8+ T cell phenotype and function, serum C-reactive protein, and in vitro, LPS-stimulated and unstimulated tumor necrosis factor-α production. Subjects aged 65-80 yrs. were assigned to either a physically active (PA, N=14) or physically inactive group (PI, N=14) based on a physical activity questionnaire and estimated VO2max. Physically inactive subjects completed 12 weeks (3d/wk) of endurance and resistance exercise training. The PA group maintained their habitual activity level and served as controls. Blood samples were obtained at baseline and following the training intervention or control period. Flow cytometry was used to determine the percentage of inflammatory monocytes and monocyte TLR4 expression, the percentage of CD8+ naïve, memory and cytotoxic T cells, along with their capacity to produce TNF-α in response to phorbol myristate acetate (PMA) stimulation. An in vitro whole blood method and an enzyme-linked immunosorbent assay (ELISA) were used to determine LPS-stimulated and unstimulated TNF-α production. At baseline, the PA group had a lower inflammatory monocyte percentage (p= 0.07) and significantly lower unstimulated TNF-α production (p< 0.05) than the PI group. Following 12 weeks of exercise training, inflammatory monocyte percentage and concentration, and Ing/m1 LPS-stimulated and unstimulated TNF-α production were significantly decreased (p< 0.05). There were no group differences or training-induced effects on monocyte TLR4 expression, but there was a tendency (p= 0.11) for training to lower monocyte TLR4. There were significant group effects such that serum CRP, the percentage of CD8+ cytotoxic T-cells staining positive for TNF-α, and lymphocyte and CD8+(cytotoxic and memory) T cell intracellular TNF-α expression were lower in the PA group compared to the PI group irrespective of time (baseline, post-training/control period). In conclusion, this research indicates that physically active subjects have a lower inflammatory status as measured by monocyte phenotype, CD8+ T cell phenotype, and unstimulated TNF-α production than physically inactive subjects. Furthermore, this is the first study to show that 12 weeks of exercise training significantly reduces inflammatory monocyte percentage in previously inactive subjects.

Degree

Ph.D.

Advisors

Flynn, Purdue University.

Subject Area

Physiology

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