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Effects of human interleukin-6 on megakaryocyte development and
thrombocytopoiesis in primates
CP Stahl, D Zucker-Franklin, BL Evatt and EF Winton
Division of Immunologic, Oncologic, and Hematologic Diseases, Centers for
Disease Control, Atlanta, GA 30333.
Recombinant human interleukin-6 (IL-6) has previously been shown to
increase platelet counts in mice and primates. To elucidate the mechanisms
underlying this phenomenon, serial analyses were performed on
megakaryocytes obtained from rhesus monkeys treated for 8 days with 30
micrograms/kg/d of recombinant human IL-6. Platelet counts increased to a
maximum of 7.8 x 10(5)/microL with biphasic peaks on days 7 and 12 without
significant changes in platelet volumes. Large increases in DNA content
were seen by two-color flow cytometry and digital image analysis. Ploidy
distribution underwent a significant shift between study days 3 and 11 (P
less than .0001) with large increases in the frequency of 64N and 128N
megakaryocytes. The modal ploidy increased from the normal 16N to 64N.
Megakaryocyte size, as measured by area, was increased 2- to 2.7-fold. On
day 3, multiple megakaryocytes were seen in endomitosis, along with an
abundance of young cells with wide, organelle-free peripheral zones. The
giant megakaryocytes seen on days 5 to 7 exhibited marked membrane
hyperplasia that occupied much of the cell. Emperipolesis occurred
frequently, as did megakaryocyte cell death. No giant platelets were seen.
We conclude that IL-6 significantly alters the process of megakaryocyte
maturation and thrombocytopoiesis, and that these effects, at least in the
doses of IL- 6 administered, should not be equated with the physiologic
mechanisms operative during accelerated platelet production.
Volume 78,
Issue 6,
pp. 1467-1475,
09/15/1991
Copyright © 1991 by The American Society of Hematology
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