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Recombinant human interleukin-11 stimulates megakaryocytopoiesis and
increases peripheral platelets in normal and splenectomized mice
TY Neben, J Loebelenz, L Hayes, K McCarthy, J Stoudemire, R Schaub and SJ Goldman
Division of Preclinical Biology, Genetics Institute, Cambridge, MA 02140.
The effects of recombinant human interleukin-11 (rhIL-11) on in vivo mouse
megakaryocytopoeisis were examined. Normal C57Bl/6 mice and splenectomized
C57Bl/6 mice were treated for 7 days with 150 micrograms/kg rhIL-11
administered subcutaneously. In normal mice, peripheral platelet counts
were elevated compared with vehicle-treated controls after 3 days of
rhIL-11 treatment and remained elevated until day 10. Splenectomized mice
treated with rhIL-11 showed elevated peripheral platelet counts that were
similar in magnitude to normal rhIL-11-treated mice. However, on day 10 the
platelet counts in rhIL-11- treated, splenectomized mice were no longer
elevated. Analysis of bone marrow megakaryocyte ploidy by two-color flow
cytometry showed an increase, relative to controls, in the percentage of
32N megakaryocytes in both normal and splenectomized animals treated with
rhIL-11. In normal mice, the number of spleen megakaryocyte colony-forming
cells (MEG-CFC) were increased twofold to threefold relative to controls
after 3 and 7 days of rhIL-11 treatment, whereas the number of bone marrow
MEG-CFC were increased only on day 7. The number of MEG-CFC in the bone
marrow of rhIL-11-treated, splenectomized mice was increased twofold
compared with controls on both days 3 and 7 of the study. These data show
that in vivo treatment of normal or splenectomized mice with rhIL-11
increased megakaryocyte progenitors, stimulated endoreplication of bone
marrow megakaryocytes, and increased peripheral platelet counts. In
addition, results in splenectomized mice showed that splenic hematopoiesis
was not essential for the observed increases in peripheral platelets in
response to rhIL-11 administration.
Volume 81,
Issue 4,
pp. 901-908,
02/15/1993
Copyright © 1993 by The American Society of Hematology
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