Nephrol Dial Transplant (1994) 9: 775-779
© 1994 European Renal Association-European Dialysis and Transplant Association
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Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro
1Renal Unit, University of Capetown and Groote Schuur Hospital Cape Town, South Africa 2MRC-UCT Liver Centre and Department of Medicine and University of Capetown and Groote Schuur Hospital Cape Town, South Africa 3Department of Pharmacology, University of Capetown and Groote Schuur Hospital Cape Town, South Africa
Decreased production of erythropoietin (Epo) as a result of reduced renal mass is considered the main factor underlying the anaemia that is invariably associated with chronic renal failure (CRF). Other mechanisms such as accumulation of inhibitors of Epo also contribute. In this study we show that supernatant from peripheral blood mononuclear cells (PBMC) cultured from patients with CRF inhibits Epo release by Hep G2 cells in vitro. Ten patients (5 male) with CRF (mean age 42 years, range 25–60) were studied. Five were approaching end-stage renal failure and five were maintained on haemodialysis (HD). Ten apparently healthy volunteers were used as controls. Full blood counts and serum Epo (RIA) levels were determined and adherent PBMC were cultured for 48 h with and without LPS. There was a significant rise in TNF-
and IL1-ß levels measured in monocyte supernatant (MS) from patients and controls after LPS stimulation (P<0.05) and in IL-l levels in patients (P<0.05). IL-1ß levels were higher in patients compared to controls both before and after stimulation with LPS (P<0.05). Hep G2 cells were cultured in 5% CO2 and 20% O2 and incubated with MS from patients and controls for 24 h. Hep G2 harvest fluids were then analysed for Epo levels, which were expressed as a function of total cell protein (mU/mg). Epo production was inhibited by MS from patients compared to controlsboth before and after stimulation with LPS (P<0.0001). There was, however, no direct correlation between the degree of Epo suppression and concentrations of MS TNF-, IL-l, and IL-ß. Inhibition byspecific polyclonal anti-TNF- antibodies and anti-IL-ß antibodies did not abrogate the inhibition ofEpo release by Hep G2 cells. These results demonstrate that although PBMC from patients with CRF produce factors that inhibit Hep G2 cell secretion of Epo in vitro, this effect does not appear to be directly related to the proinflammatory cytokines TNF-, IL-l, and IL-ß.
Keywords: chronic renal failure; erythropoietin; haemodialysis; periphral blood monocytes; tumour necrosis factor; interleukin-1
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  C. Mora, M. Macia, and J. F. Navarro Renal failure, anaemia, cytokines and inflammation Nephrol. Dial. Transplant., July 1, 2001; 16(7): 1524 - 1525. [Full Text] [PDF]
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