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Transcript
1830
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
1
School 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 (IL6) 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). Bacteriastimulated 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.