Skeletal muscle, cytokines, and oxidative stress in end-stage renal disease.
BACKGROUND
End-stage renal disease (ESRD) is a state of microinflammation, with increased activation of cytokines and augmented oxidative stress. While peripheral blood mononuclear cells are an established source of reactive oxygen species and inflammatory cytokines during hemodialysis (HD), skeletal muscle is also capable of generating these biomolecules.


METHODS
Femoral arterio-venous (A-V) balance of interleukin-1 (IL-1), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), malonyldialdehyde (MDA), and carbonyl protein (CP) were measured in 17 ESRD patients and 9 healthy volunteers. ESRD patients were studied before (pre-HD) and during HD. mRNA levels of cytokines, heme oxygenase-1 (HO-1), and suppressors of cytokine signaling-2 (SOCS-2) were quantitated in the skeletal muscle by real-time polymerase chain reaction (PCR).


RESULTS
Arterial concentration of MDA (pmol/mL) was higher pre-HD (325.5 +/- 19.6) compared to controls (267.7 +/- 14.7), but decreased intradialysis (248.8 +/- 16.1) (P < 0.01). Dialysis clearance of MDA was 16.9 +/- 3.1 mL/min. CP concentration (nmol/mg protein) in the artery was significantly higher pre-HD (2.29 +/- 0.09) than in controls (1.92 +/- 0.05), and remained stable during HD (2.23 +/- 0.07). Plasma cytokines increased to a variable degree in the artery and vein during HD. A-V balance studies demonstrated that the MDA (17.8%) and CP (5.1%) concentrations increased significantly in the vein intradialysis. Venous concentration of IL-6 was higher than that in the artery during dialysis (16.27 +/- 2.42 vs. 11.29 +/- 2.17 pg/dL, P < 0.01). mRNA levels of IL-6 (0.028 +/- 0.02 vs. 6.69 +/- 0.21), HO-1 (0.96 +/- 0.01 vs. 5.08 +/- 1.11), and SOCS-2 (0.63 +/- 0.12 vs. 0.82 +/- 0.14) in the muscle increased during HD (P < 0.01). Immunohistochemical studies confirmed the increase in IL-6 protein in the skeletal muscle during HD. The intradialytic increase in IL-1, IL-10, and TNF-alpha gene expression was not significant.


CONCLUSIONS
Skeletal muscle may also contribute to the circulating plasma IL-6 and increased oxidative stress during HD.
Raj
Dominic S C
DS
Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, 87131, USA. draj@salud.unm.edu
Dominic
Elizabeth A
EA
Pai
Amy
A
Osman
Farid
F
Morgan
Marilee
M
Pickett
Gavin
G
Shah
Vallabh O
VO
Ferrando
Arny
A
Moseley
Pope
P
D000328:Adult; D001706:Biopsy; D001798:Blood Proteins / Q000378:metabolism; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D006977:Hypertension, Renal / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000378:metabolism*; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D001798:Blood Proteins; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008315:Malondialdehyde