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Effects of injected leukemia inhibitory factor on hematopoietic and other
tissues in mice
D Metcalf, NA Nicola and DP Gearing
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne
Hospital, Victoria, Australia.
Purified bacterially synthesized recombinant murine leukemia inhibitory
factor (LIF) was injected in varying doses for up to 2 weeks into adult
DBA/2 and C3H/HeJ mice. At high doses (2 micrograms, three times daily) LIF
exhibited toxic effects seen as behavioral changes, loss of body fat, and
thymus atrophy. Dose-related rises were observed in blood platelets,
erythrocyte sedimentation rates, and serum calcium to albumin ratios,
including dose schedules with no toxic effects. LIF induced a decrease in
bone marrow cell numbers, particularly in marrow lymphocytes, and a
moderate increase in spleen weight with a reduction in spleen lymphocytes
and an elevation of erythroid populations. LIF- injected mice showed a rise
in megakaryocytes up to twofold in the marrow and fivefold in the spleen,
with an associated 10-fold rise in megakaryocyte progenitor cells in the
spleen. Comparable rises in other types of progenitor cells were also
observed in the spleen. The observed changes indicate the biologic activity
of LIF in vivo and are consistent with the known wide range of in vitro
actions of this molecule. The ability of LIF to elevate megakaryocyte and
platelet levels suggests a potential clinical application of LIF in the
treatment of thrombocytopenias.
Volume 76,
Issue 1,
pp. 50-56,
07/01/1990
Copyright © 1990 by The American Society of Hematology
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