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Murine autoimmune hemolytic anemia resulting from Fc gamma receptor-
mediated erythrophagocytosis: protection by erythropoietin but not by
interleukin-3, and aggravation by granulocyte-macrophage colony-
stimulating factor
T Berney, T Shibata, R Merino, Y Chicheportiche, V Kindler, P Vassalli and S Izui
Department of Pathology, University of Geneva, Switzerland.
We have evaluated the therapeutic activity of recombinant erythropoietin
(rEpo), in comparison with recombinant interleukin-3 (rIL-3) and
granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal
form of acute anemia resulting from Fc gamma receptor- mediated
erythrophagocytosis after a single injection (500 micrograms) of a
monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous
perfusion of rEpo before the administration of anti-MRBC monoclonal
antibody completely protected animals from death due to anemia with a rapid
recovery, while no protection was obtained by rIL-3 perfusion. In contrast,
rGM-CSF perfusion markedly accelerated the progression of anemia and the
mortality rate. This was found to result from an enhancement of
erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes
that massively infiltrated the livers. Even after the injection of a
sublethal dose (100 micrograms) of anti- MRBC monoclonal antibody,
rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore,
we have shown that rEpo was able to treat efficiently a spontaneous form of
autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas
rGM-CSF markedly aggravated anemia. This may be of clinical importance,
because GM-CSF administration could exhibit an adverse effect in some
autoimmune diseases that involve autoimmune anemia.
Volume 79,
Issue 11,
pp. 2960-2964,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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