Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state

Kidney Int. 2006 Jul;70(2):384-90. doi: 10.1038/ Epub 2006 Jun 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arteries
  • Biopsy
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Female
  • Forearm / blood supply
  • Gene Expression / immunology
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Interleukin-1 / blood
  • Interleukin-10 / blood
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism*
  • Male
  • Middle Aged
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / pathology
  • Phenylalanine / metabolism
  • RNA, Messenger / metabolism
  • Renal Insufficiency, Chronic / immunology*
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / physiopathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Uremia / immunology
  • Uremia / metabolism
  • Veins


  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Phenylalanine