Multiple in vivo effects of interleukin-3 and interleukin-6 on murine
megakaryocytopoiesis
PA Carrington, RJ Hill, PE Stenberg, J Levin, L Corash, J Schreurs, G Baker and FC Levin
Department of Laboratory Medicine, University of California School of
Medicine, San Francisco.
The in vivo effects of interleukin-3 (IL-3), interleukin-6 (IL-6), and a
combination of IL-3 plus IL-6 on murine megakaryocytopoiesis and
thrombopoiesis were examined. Human recombinant IL-6 was administered
subcutaneously as 14 equal injections of 5,000 units each during a 102-
hour period. Murine recombinant IL-3 was given as 8 injections of 80,000
units each during the first 54 hours. Megakaryopoiesis and thrombopoiesis
were evaluated 120 hours after initial administration of the cytokines.
Platelet levels increased by 20% following IL-3 alone, 35% following IL-6
alone and 61% after administration of both IL-3 and IL-6. Platelet
production, as measured by 75Se-selenomethionine incorporation, increased
by approximately 120% in animals that had received IL-6 or IL-3 plus IL-6.
Megakaryocyte ploidy analysis by two- color flow cytometry showed a shift
in the modal ploidy class from 16N to 32N and a significant increase in the
frequency of 64N cells only in IL-6 treated animals. Both bone marrow and
splenic megakaryocyte colony- forming cells were significantly increased
following either IL-3 or IL- 6. Bone marrow megakaryocyte size increased
18%, 43%, and 38%, respectively, after administration of IL-3, IL-6, or the
combination of IL-3 plus IL-6. Leukocyte counts and hematocrits were
unaffected by either cytokine. Additional groups of mice received the same
injection schedule as above and the serial effects on peripheral blood cell
levels were assessed for 30 days. Platelet levels, which had been elevated
by IL-3 or IL-6, fell to control values within 4 days following the last
injection. Animals given IL-6 or IL-3 plus IL-6 were subsequently
thrombocytopenic relative to controls on days 7 through 9 following
cessation of treatment. Temporary 'cycling' of platelet levels was observed
for 3 weeks following treatment with IL-6 or the combination of IL-3 plus
IL-6. We conclude that IL-6 and to a lesser extent IL-3 stimulate platelet
production in vivo and that their combined effects on platelet levels are
approximately additive. Following discontinuation of IL-3 or IL-6, the
effects are rapidly reversed, presumably by negative feedback mechanisms,
resulting in a period of 'rebound thrombocytopenia' in mice that had
received IL-6.
Volume 77,
Issue 1,
pp. 34-41,
01/01/1991
Copyright © 1991 by The American Society of Hematology
