Diminished erythropoietin-induced erythroid growth in patients with renal anemia is restored by recombinant human erythroid differentiation factor.
An examination of the in vitro sensitivity of marrow burst-forming units for erythroid (BFU-E) to various concentrations of human recombinant erythropoietin (rEpo) and interleukin-3 (IL-3, 20 ng/mL) in serum-deprived methylcellulose cultures revealed that cells obtained from patients with chronic renal failure showed a defective response to rEpo, particularly at lower concentrations. This poor response was not corrected by the addition of neutralizing antibodies to antitumor necrosis factor-alpha or antiinterleukin-1 alpha/beta. When purified CD34+ cells from these patients were tested for dose-dependent growth to rEpo, the curve resembled that of normal donors, indicating that there was an intrinsic defect in the patients' progenitor/accessory cell interactions. Using unseparated cells from the patients, we then tested whether the interaction between erythroid differentiation factor (EDF) and rEpo affected BFU-E growth. Although EDF, either alone or in combination with IL-3, did not affect the growth of BFU-E in the absence of rEpo, the reduced sensitivity to rEpo in the patients was brought closer to normal limits by the addition of 10 ng/mL EDF to the cultures. The present results may suggest the possibility that, in patients with renal anemia, concomitant administration of EDF may increase the therapeutic ratio of rEpo therapy by enhancing the sensitivity of progenitor cells to rEpo, thereby decreasing the therapeutic dose of costly rEpo.
Shimizu
T
T
Department of Pediatrics, Kurume University, Japan.
Kawano
Y
Y
Takaue
Y
Y
Kuroda
Y
Y
D028341:Activins; D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000097:blood* / Q000209:etiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology
D007377:Interleukin-3; D011994:Recombinant Proteins; D028341:Activins; D004921:Erythropoietin; D007265:Inhibins