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Preclinical analysis of cytokine therapy in the SCID-hu mouse
S Kyoizumi, LJ Murray and R Namikawa
SyStemix Inc., Palo Alto, CA 94303.
A severe combined immunodeficient (SCID)-hu mouse model implanted with
human fetal bone was used to assess the effects of various recombinant
human (rh) hematopoietic growth factors, administered either alone or in
combination, on human hematopoiesis in vivo. Treatment with rh granulocyte
colony-stimulating factor (G-CSF) elicited the expansion of mature
neutrophilic granulocyte populations in human marrow. Administration of rh
interleukin-3 (IL-3) induced significant increases of eosinophilic
granulocyte and burst-forming unit, erythrocyte (BFU-E) activity. The
rhIL-6 did not cause significant changes in the subpopulations of human
hematopoietic cells within the grafts, but did increase the number of
colony-forming unit, granulocyte-macrophage and BFU-E. Pretreatment with
rhIL-3 followed by rh erythropoietin (Epo) administration enhanced
Epo-induced human erythropoiesis significantly. No synergistic effects on
myelopoiesis were observed using sequential treatment with rhIL-3 followed
by rhG-CSF. Instead, these factors seemed to work independently, with
rhG-CSF increasing the percentage of neutrophils and rhIL-3 increasing the
percentage of eosinophils. When administered simultaneously with rhEpo,
rhIL-6 showed dose-dependent inhibitory effects on in vivo Epo-induced
human erythropoiesis. The rhIL-6 also caused a reduction in the percentage
of human neutrophils induced by rhG-CSF. These results suggest that the
SCID-hu mouse provides a useful small animal model to assess the in vivo
effects of hematopoietic growth factors on human hematopoiesis.
Volume 81,
Issue 6,
pp. 1479-1488,
03/15/1993
Copyright © 1993 by The American Society of Hematology
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