Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro |
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| Authors: | Cassidy, M.J.D. Jager, C.De Ebrahim, O. Camachio, P. Robson, S. |
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| Affiliation: | 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 |
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| Abstract: | Decreased production of erythropoietin (Epo) as a result ofreduced renal mass is considered the main factor underlyingthe anaemia that is invariably associated with chronic renalfailure (CRF). Other mechanisms such as accumulation of inhibitorsof Epo also contribute. In this study we show that supernatantfrom peripheral blood mononuclear cells (PBMC) cultured frompatients with CRF inhibits Epo release by Hep G2 cells in vitro.Ten patients (5 male) with CRF (mean age 42 years, range 2560)were studied. Five were approaching end-stage renal failureand five were maintained on haemodialysis (HD). Ten apparentlyhealthy volunteers were used as controls. Full blood countsand serum Epo (RIA) levels were determined and adherent PBMCwere cultured for 48 h with and without LPS. There was a significantrise in TNF- and IL1-ß levels measured in monocytesupernatant (MS) from patients and controls after LPS stimulation(P<0.05) and in IL-l levels in patients (P<0.05). IL-1ßlevels were higher in patients compared to controls both beforeand after stimulation with LPS (P<0.05). Hep G2 cells werecultured in 5% CO2 and 20% O2 and incubated with MS from patientsand controls for 24 h. Hep G2 harvest fluids were then analysedfor Epo levels, which were expressed as a function of totalcell protein (mU/mg). Epo production was inhibited by MS frompatients compared to controlsboth before and after stimulationwith LPS (P<0.0001). There was, however, no direct correlationbetween the degree of Epo suppression and concentrations ofMS TNF-, IL-l, and IL-ß. Inhibition byspecific polyclonalanti-TNF- antibodies and anti-IL-ß antibodies didnot abrogate the inhibition ofEpo release by Hep G2 cells. Theseresults demonstrate that although PBMC from patients with CRFproduce factors that inhibit Hep G2 cell secretion of Epo invitro, this effect does not appear to be directly related tothe proinflammatory cytokines TNF-, IL-l, and IL-ß. |
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| Keywords: | chronic renal failure erythropoietin haemodialysis periphral blood monocytes tumour necrosis factor interleukin-1 |
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