NDT Advance Access originally published online on October 19, 2004
Nephrology Dialysis Transplantation 2004 19(12):3078-3083; doi:10.1093/ndt/gfh491
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Nephrol Dial Transplant Vol. 19 No. 12 © ERA-EDTA 2004; all rights reserved
Original Article
Impaired release of interleukin-6 from human osteoblastic cells in the uraemic milieu
1 Department of Renal Medicine and Transplantation, Bart's and the Royal London Hospitals, London, 3 Department of Endocrinology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary University of London, 4 Department of Nephrology, University College London Hospitals, The Middlesex Hospital, London and 3 Department of Renal Medicine and Centre for Integrated Systems Biology and Medicine, Derby City General Hospital, Derby, UK
Correspondence and offprint requests to: Professor John Cunningham, Department of Nephrology, University College London Hospitals, The Middlesex Hospital, Mortimer St, London W1T 3AA, UK. Email: john.cunningham{at}uclh.org
Background. Osteoblast-derived interleukin-6 (IL-6) affects bone metabolism and is linked with a number of pathological states characterized by increased bone resorption, including osteoporosis and renal osteodystrophy. To examine the possibility that uraemia directly influences the release of this cytokine in bone, we have investigated the effect of human uraemic serum on the release of IL-6 from human osteoblast-like cells.
Methods. Individual serum samples collected from healthy male volunteers or male haemodialysis patients prior to and during a dialysis treatment were assayed for IL-6, interleukin-1ß (IL-1ß) and soluble IL-6 receptor (sIL-6R) using specific enzyme-linked immunosorbent assays. MG-63 and SaOS-2 cells were cultured in media containing pooled sera from both groups and alongside matching charcoal-stripped sera. IL-6 concentrations were determined in harvested cell supernatants after 24 h. In further experiments, media containing individual sera obtained from five patients at regular intervals during their haemodialysis treatment were incubated with MG-63 cells to determine the effects of the dialysis process on IL-6 secretion.
Results. Haemodialysis patients had significantly higher (n = 10, P<0.001) circulating concentrations of IL-6 (7.0±1.6 pg/ml) than normal subjects (0.4± 0.1 pg/ml), but there were no significant differences in the concentrations of either IL-1ß or sIL-6R. These serum concentrations did not change significantly during 80 min of dialysis. IL-6 release by MG-63 cells incubated with charcoal-stripped serum from normal or from uraemic subjects was similar. Incubation with untreated sera from normal subjects increased IL-6 release by 
6-fold above the charcoal-stripped control, whereas sera from uraemic subjects increased IL-6 release by only 2- to 3-fold (normal vs uraemic of 6878±595 and 2579±169 pg/ml, respectively, P<0.001). Similar results were seen with SaOS-2 cells. Haemodialysis did not restore the capacity of uraemic serum to augment IL-6 release to the same degree as normal serum.
Conclusions. These data show that the augmentation of IL-6 release from human osteoblastic cells after incubation with normal serum is greater than after uraemic serum. This may indicate the presence of an inhibitor of IL-6 release in uraemic serum that is involved in the deranged bone turnover of uraemic patients.
Keywords: bone remodelling; haemodialysis; interleukin-6; osteoblast; renal osteodystrophy; uraemic serum
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