Evidence for anti-inflammatory effects of exercise in CKD

Abstract

CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert anti-inflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD.

Figure 1.

Effects of regular exercise on expression of SEB-stimulated immune cell activation markers. Relative changes over 6 months in SEB-stimulated CD69 expression by CD4⁺CD69⁺ or CD8⁺CD69⁺ lymphocytes (left panel) and SEB-stimulated CD86 or HLA-DR expression by CD14⁺CD86⁺HLA-DR⁺ monocytes (right panel) for the exercise (white bars) and control (black bars) groups. Data are mean±SEM (n=13 exercise group; n=11 control group). GMFI, geometric mean of fluorescence intensity.

Figure 2.

Effects of regular exercise on plasma IL-6 to IL-10 ratio at baseline and 6 months for each group. Data are individual values (n=13 exercise group; n=11 control group). Time×group interaction: P=0.001.