Comparative effects of thrombopoietin and interleukin-6 on murine
megakaryocytopoiesis and platelet production
TP McDonald, MB Cottrell, CJ Swearingen and RE Clift
Department of Animal Science, University of Tennessee, College of
Veterinary Medicine, Knoxville 37901-1071.
A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) derived
from human embryonic kidney (HEK) cells is known to increase platelet
production and to increase the number of morphologically unrecognizable
early megakaryocytes, ie, small acetylcholinesterase-positive (SAChE+)
cells in mice. Other recent studies have concluded that interleukin-6
(IL-6) also stimulates murine megakaryocytopoiesis both in vitro and in
vivo. Some workers have suggested that IL-6 is thrombopoietin. Therefore,
the purpose of this study was to compare the effects of TSF and IL-6 on
percent 35S incorporation into platelets, platelet sizes, and the
percentages of SAChE+ cells in C3H mice, and to determine if they produce
the same or different responses. The results showed that two or four
injections of a partially purified TSF (total dose of 2 or 4 units (U) over
a 1- or 2-day period) increased percent 35S incorporation into platelets (P
less than .005) and platelet sizes (P less than .005) of both normal and
rebound-thrombocytotic mice when compared with values from other mice
treated with human serum albumin, the carrier protein for both TSF and
IL-6. In eight separate experiments, it was shown that IL-6 (40,000 U, 4
micrograms), when given to rebound-thrombocytotic mice in four injections
over a 2-day period, produced a small but significant (P less than .005)
increase in percent 35S incorporation into platelets. Additional studies
showed that negative results were obtained when similar high doses of IL-6
were administered in two doses over a 1-day period. TSF, but not IL-6,
stimulated an increase in platelet sizes of normal mice (P less than .005
to 0.0005); however, IL-6 increased platelet sizes of rebound-
thrombocytotic mice when given in two of four injections (P less than .05
to .0005). Also, IL-6, but not TSF, caused anemia in normal mice (P less
than .0005) that were given two injections and tested 3 days later. TSF
stimulated an increase (P less than .005) in the percentage of SA-ChE+
cells; whereas IL-6, even at high doses, did not. Because of the observed
differences in biologic responses of these two cytokines, we conclude that
TSF and IL-6 are separate entities.
Volume 77,
Issue 4,
pp. 735-740,
02/15/1991
Copyright © 1991 by The American Society of Hematology
