Interleukin-6 modulates hepatic and muscle protein synthesis during hemodialysis.
Increased demand for amino acids to sustain acute-phase protein synthesis could be the stimulus for the increased muscle protein catabolism during hemodialysis (HD). This could be attenuated by intradialytic amino-acid infusion. To test this, we measured the fractional synthesis rates of albumin, fibrinogen, and muscle protein in eight patients with end-stage renal disease at baseline before dialysis and during HD without or with amino-acid infusion. The percentage change in the fractional synthesis rates of albumin, fibrinogen, and muscle protein from baseline was significantly higher during HD with amino-acid infusion than without amino-acid infusion. Leg muscle proteolysis was significantly increased during unsupplemented HD compared with baseline, but this was not decreased by amino-acid infusion. Arteriovenous balance studies across the leg showed a net efflux of interleukin-6 (IL-6) from the muscle into the vein during HD. The fractional synthesis rate of albumin, fibrinogen, and muscle protein correlated with each other and with the IL-6 efflux from the leg. Leg muscle protein catabolism was positively related to IL-6 release from the leg and not associated with amino-acid availability. Our results show that intradialytic cytokine activation and not amino-acid depletion is the major protein catabolic signal during HD.
Raj
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DS
Division of Nephrology and Epidemiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-5271, USA. draj@salud.unm.edu
Moseley
P
P
Dominic
E A
EA
Onime
A
A
Tzamaloukas
A H
AH
Boyd
A
A
Shah
V O
VO
Glew
R
R
Wolfe
R
R
Ferrando
A
A
D000328:Adult; D000418:Albumins / Q000096:biosynthesis*; D000596:Amino Acids / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D006435:Renal Dialysis
D000418:Albumins; D000596:Amino Acids; D016207:Cytokines; D015850:Interleukin-6; D009124:Muscle Proteins; D005340:Fibrinogen