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EXERCISE DURING HAEMODIALYSIS: THE ACUTE EFFECTS ON MARKERS OF SYSTEMIC INFLAMMATION AND NEUTROPHIL DEGRANULATION
Maurice Dungey1, 2, Nicolette C Bishop1, Hannah ML Young2, James O Burton2 & Alice C Smith2
1School of Sport, Exercise and Health Sciences, Loughborough University, United Kingdom 2Leicester Kidney Exercise Team, John Walls’ Renal Unit, University Hospitals of Leicester NHS Trust, United Kingdom
BACKGROUND: End-stage renal disease patients requiring haemodialysis (HD) frequently present with chronic inflammation and are in a state of immune dysfunction. Alterations in inflammatory interleukins, TNF-α and neutrophil degranulation are implicated in the pathogenesis of cardiovascular disease, and associated with all-cause mortality. In healthy individuals regular physical activity may improve markers of inflammation whereby an acute bout of exercise is purported to induce myocyte secretion of interleukin-6 (IL-6) and a subsequent anti-inflammatory cytokine cascade. To our knowledge there is no evidence of the acute effect of exercise during HD on inflammatory markers or immune function. This study aimed to examine the acute effect of exercise during HD on cytokines involved in inflammation and neutrophil response to bacterial stimulation.
METHODS: The acute effects of exercise were studied in 13 HD patients familiar to regular exercise during HD (age: 59.2 ± 10.4 years) using a randomised crossover design with patients acting as their own controls. In the control group patients rested throughout HD. In the exercise group, 60 minutes after the commencement of HD, patients cycled for 30 min at a “somewhat hard” intensity (rating of perceived exertion 13). Circulating concentrations of IL-6, IL-10, IL-1ra and TNF-α were measured using ELISA at the following time points: immediately pre- and post-exercise, 1h post-exercise and at the end of dialysis (or equivalent times during control). Neutrophil degranulation was measured using elastase ELISA in blood that had and had not been subjected to bacterial stimulation at pre- and post-exercise and at the end of dialysis. All values were adjusted for changes in plasma volume.
RESULTS: IL-6 concentrations were significantly higher at the end of dialysis than at earlier time points in both groups (4.98 ± 2.94 to 7.92 ± 3.64 pg/mL; P = 0.03), but concentrations did not differ between exercisers and controls.
In both groups TNF-α decreased during HD (from 3.58 ± 1.46 to 2.65 ± 1.14 pg/mL; P = 0.03). There was a trend towards greater reductions in TNF-α concentrations in the exercise group compared to controls by the end of dialysis (4.13 ± 1.70 to 2.49 ± 1.09 pg/mL vs. 3.03 ± 0.91 to 2.81 ± 1.23 pg/mL respectively; P = 0.05).
IL-10 levels were significantly lower at the end of dialysis in the exercise group compared with the control group (0.38 ± 0.38 vs. 0.68 ± 0.34 pg/mL, P = 0.02). No significant effects on IL-1ra concentrations were seen between exercise and control groups at any time point (P > 0.30 in all cases). Spontaneous neutrophil degranulation increased during HD in both groups (144 ± 109 to 169 ± 149 ng/mL; P = 0.04). Bacteria-stimulated neutrophil degranulation was not significantly different between groups even after adjusting for the number of neutrophils (P = 0.11).
CONCLUSION: HD treatment caused an increase in circulating levels of the inflammatory cytokine IL-6 and neutrophil degranulation. Exercise at an intensity tolerated by HD patients appeared to be insufficient to stimulate significant myocyte IL-6 secretion. Exercise may suppress TNF-α secretion and this may explain divergent IL-10 concentrations at the end of dialysis, but the mechanisms are unclear and require further investigation. In conclusion, intradialytic exercise does not appear to exacerbate HD induced inflammation.