Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state.
To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P<0.004) in HD patients. Both IL-6 protein and IL-6 mRNA expression were increased in muscle of inflamed CKD patients vs controls (P<0.05). Although muscle net protein balance was similar in all patients, it was significantly more negative in HD patients with high than in those with low IL-6 plasma levels (P<0.05). In addition, net protein balance was related to the forearm release of IL-6 in HD patients only (r=0.47; P<0.038). These data demonstrate that IL-6 expression is upregulated in muscle, and that muscle tissue, by releasing this cytokine, may contribute to the inflammatory response in HD patients. The release of IL-6 from peripheral tissues is associated with an increase in muscle protein loss in HD patients, suggesting that muscle release of IL-6 is linked to protein catabolism in these patients. The release of IL-6 from peripheral tissues may act as a signal for the inflammatory response and contribute to functional dysregulation in uremia.
Garibotto
G
G
Department of Internal Medicine, Nephrology Division, Genoa University, Genoa, Italy. gari@unige.it
Sofia
A
A
Procopio
V
V
Villaggio
B
B
Tarroni
A
A
Di Martino
M
M
Cappelli
V
V
Gandolfo
M T
MT
Aloisi
F
F
De Cian
F
F
Sala
M R
MR
Verzola
D
D
D000368:Aged; D001158:Arteries; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology; D010649:Phenylalanine / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014511:Uremia / Q000276:immunology / Q000378:metabolism; D014680:Veins
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010649:Phenylalanine