CONTAMINATION OF ERYTHROPOIETIN BY ENDOTOXIN - INVIVO AND INVITRO EFFECTS ON MURINE ERYTHROPOIESIS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 54  (1) , 146-158
Abstract
Endotoxin was detected in all erythropoietin preparations tested and was removed from 4 lots without loss of erythropoietic activity by adsorption with limulus amebocyte lysate. Comparison of adsorbed (endotoxin-depleted) and nonadsorbed (endotoxin-containing) erythropoietin preparations demonstrated significant inhibition of CFU-e [erythroid colony-forming units] and BFU-e [erythropoietic burst-forming units] in vitro by nonadsorbed erythropoietin at concentrations higher than 0.25 U[units]/ml and 2.0 U/ml, respectively. CFU-e and BFU-e were inhibited significantly by readdition in vitro of 10-5-10-3 .mu.g of endotoxin per unit of limulus-adsorbed erythropoietin. Administration of saline or 6 U of nonadsorbed or adsorbed erythropoietin twice a day for 4 days of CF1 mice resulted in reticulocyte counts of 2.1, 9.9 and 15.9%, respectively. Nonadsorbed erythropoietin resulted in a 29% decrease in erythropoiesis, a 42% decrease in CFU-e and a 16% increase in granulopoiesis in the marrow; adsorbed erythropoietin caused a 28% increase in erythropoiesis, no significant change in CFU-e and a 19% decrease in granulopoiesis in the marrow. Both preparation resulted in marked increases in splenic erythropoiesis and granulopoiesis. The effects of adsorbed erythropoietin were similar to those produced following stimulation of hematopoiesis by endogenous erythropoietin. Hemopoietic changes induced by nonadsorbed erythropoietin in vivo and in vitro were affected substantially by contamination of the erythropoietin preparations with endotoxin.