Circulating Burst-Forming-Unit Erythroid and the Responsiveness to Recombinant Human Erythropoietin in Patients on Regular Hemodialytic Treatment

Brunati, C; Cappellini, Maria-Domenica; Feo, T. De; Stefanoni, I.; Civati, G; Ballerini, Luigi; Fiorelli, G.; Minetti, L

doi:10.1159/000187024

Cited by 3 publications

(1 citation statement)

References 14 publications

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“…This hypothesis was ad vanced also in a recent study of our group [25]. However, it is not known if Epo can physiologically stimulate the production of burst-promoting interleukins.…”

Section: Amino Acidmentioning

confidence: 68%

Uremic Inhibitors of Erythropoiesis: A Study during Treatment with Recombinant Human Erythropoietin

et al. 1992

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The effects of increasing amounts of uremic sera (US) on the growth of erythroid progenitor cells [burst-forming unit erythroid (BFU-E)] collected from peripheral blood of normal subjects were evaluated to assess the potential role of uremic inhibitors of erythropoiesis during a treatment with recombinant human erythropoietin (r-HuEpo). US were collected from 8 patients on regular dialysis with marked anemia (Hb 6 ± 0.5 g%) before and after a treatment with high doses of r-HuEpo (from 300 to 525 U/kg/week). Standard cultures for BFU-E were performed in a-metylcellulose with fetal calf serum (FCS) and 4 U/ml of r-HuEpo (Cilag, Ortho). In successive cultures, US were added at increasing amounts to the standard culture in order to assess a possible inhibitory effect on BFU-E growth. Finally, in order to assess a possible lack of stimulatory factors, we partially substituted FCS with US. The addition of US collected either before or after therapy with r-HuEpo to the standard culture had no effect on the growth of BFU-E. Vice versa, the number of cultured BFU-E decreased when FCS was partially substituted with US collected before r-HuEpo. This effect was not evident when FCS was partially substituted with US collected after r-HuEpo. No significant differences were recorded in the tested sera collected before and after therapy considering erythropoietin levels and amino acid levels. We hypothesized that some other factors with erythropoietic stimulatory activity (burst-promoting activity?) may be deficient in uremic patients with marked anemia and can be induced during therapy with r-HuEpo.

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“…This hypothesis was ad vanced also in a recent study of our group [25]. However, it is not known if Epo can physiologically stimulate the production of burst-promoting interleukins.…”

Section: Amino Acidmentioning

confidence: 68%

Uremic Inhibitors of Erythropoiesis: A Study during Treatment with Recombinant Human Erythropoietin

et al. 1992

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Circulating haematopoietic progenitors during treatment of renal anaemia with recombinant human erythropoietin

Göbel

Hoffmann

Braun³

et al. 1994

Eur J Pediatr

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The effect of recombinant human erythropoietin (rhEPO) and interleukin 3 (IL3) on circulating haematopoietic progenitors consisting mainly of immature burst-forming-units-erythrocytes (BFU-E), was investigated in ten paediatric patients treated by regular haemodialysis. During a 30-week study rhEPO treatment resulted in a rise of median haemoglobin levels from 6.7 g/dl to > 10 g/dl in all patients. Before initiating rhEPO treatment the number of circulating BFU-E in chronic renal failure patients responded to grading doses of rhEPO in vitro similar to that in control children; however, the dose-response curves were not predictive for the in vivo response to rhEPO. After an initial rise in five patients BFU-E numbers declined by week 30 of rhEPO treatment. BFU-E numbers decreased to 35% of pretreatment values. The number of granulocyte-macrophage colony forming cells (GM-CFC) also decreased during rhEPO treatment. Addition of IL3 to the culture medium containing saturating concentrations of granulocyte-macrophage colony stimulating factor did not stimulate BFU-E numbers of patients before rhEPO treatment or those of controls. However, 2 weeks after start of rhEPO treatment IL3 increased the growth of patient's BFU-E in vitro to 220% of pretreatment levels, followed by a gradual decrease of stimulation until the end of observation. These findings indicate that: (1) long-term recruitment of circulating haematopoietic progenitors during rhEPO treatment is low in children with renal anaemia; (2) rhEPO sensitivity of circulating BFU-E is not predictive for the in vivo response; (3) rhEPO treatment results in enhanced sensitivity of BFU-E to IL3.

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Stimulation of Interleukin-1 ß Production may be Involved in Unresponsiveness to Erythropoietin Therapy

1996

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Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1 beta, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 beta production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 beta during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 beta, and there was a significant difference between the two groups. Induction of IL-1 beta by rHuEPO may be one cause of persistent anemia in dialysis patients.

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Circulating Burst-Forming-Unit Erythroid and the Responsiveness to Recombinant Human Erythropoietin in Patients on Regular Hemodialytic Treatment

Cited by 3 publications

References 14 publications

Uremic Inhibitors of Erythropoiesis: A Study during Treatment with Recombinant Human Erythropoietin

Uremic Inhibitors of Erythropoiesis: A Study during Treatment with Recombinant Human Erythropoietin

Circulating haematopoietic progenitors during treatment of renal anaemia with recombinant human erythropoietin

Stimulation of Interleukin-1 ß Production may be Involved in Unresponsiveness to Erythropoietin Therapy

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