Contamination of erythropoietin by endotoxin: in vivo and in vitro effects
on murine erythropoiesis
KS Zuckerman, PJ Quesenberry, J Levin and R Sullivan
Endotoxin was detected in all erythropoietin preparations tested and was
removed from four 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 and BFU-e in
vitro by nonadsorbed erythropoietin at concentrations higher than 0.25 U/ml
and 2.0 U/ml, respectively. CFU-e and BFU-e were inhibited significantly by
readdition in vitro of 10(-5)-10(-3) mug 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,
whereas adsorbed erythropoietin caused a 28% increase in erythropoiesis, no
significant change in CFU-e and a 19% decrease in granulopoiesis in the
marrow. Both preparations resulted in marked increases in splenic
erythropoiesis and granulopoiesis. The effects of adsorbed erythropoietin
are similar to those produced following stimulation of hematopoiesis by
endogenous erythropoietin. Hemopoietic changes induced by nonadsorbed
erythropoietin in vivo and in vitro are affected substantially by
contamination of the erythropoietin preparations with endotoxin.
Volume 54,
Issue 1,
pp. 146-158,
07/01/1979
Copyright © 1979 by The American Society of Hematology
