Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible
implication of IL-6
H Kimura, T Ishibashi, Y Shikama, A Okano, Y Akiyama, T Uchida and Y Maruyama
First Department of Internal Medicine, Fukushima Medical College, Japan.
We administered recombinant human interleukin-1 beta (IL-1 beta), the
common mediator of inflammation process, to C57B1/6 male mice (0.5
microgram, every 12 hours over five times) intraperitoneally and
consequently induced a remarkable thrombocytosis. Day 1 was designated as
the following day of the last injection in the morning. A significant
thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162
+/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1
beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow
megakaryocytes was noted on days 1 and 2. The incorporation of
75Se-selenomethionine into circulating platelets as a measure of platelet
production was about 2.3 times higher in IL-1 beta-treated mice than in
control mice. To determine which factor(s) is responsible for elicited
thrombocytosis, the in vitro studies and bioassays for several
hematopoietic factors were performed. IL-1 beta by itself did not stimulate
megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is
attributed to other factor(s) via IL-1 beta stimulation. Serum
colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5
microgram) injection, monitored by colony assay with 10% tested serum,
peaked at 3 hours. Formed colonies were mostly granulocyte (G) and
granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse
GM-CSF serum or using human marrow as target cells showed that the CSF
activity of the tested serum consisted of, at least, GM-CSF and G-CSF.
Addition of IL-3 concomitantly with the tested serum gave rise to a greater
number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent
cell line 32D clone 5, and erythropoietin activities were not detected at
serum level in IL-1 beta-treated mice. Serum IL-6 assay by IL-6- dependent
mouse hybridoma cell line MH-60.BSF2 showed high levels of the tested serum
with a peak at 2.5 hours with no detection at 10 hours after the injection.
Heated IL-1 beta caused an increase of neither IL- 6 nor CSF activities.
Our data suggest that the thrombocytosis induced by IL-1 beta is mediated
by IL-6 or a combination of IL-6 and other cytokine(s), and that IL-6 may
play a regulatory role in platelet production in vivo.
Volume 76,
Issue 12,
pp. 2493-2500,
12/15/1990
Copyright © 1990 by The American Society of Hematology
