We administered recombinant human interleukin-1β (IL-1β), the common mediator of inflammation process, to C57B1/6 male mice (0.5 μg, 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 × 104/mm3) compared with the control mice injected with heated IL-1β (101 ± 11 × 104/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Seselenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1β-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-1β by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1β stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1β (0.5 μg) 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-1β-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-1β caused an increase of neither IL-6 nor CSF activities. Our data suggest that the thrombocytosis induced by IL-1β 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. © 1990 by The American Society of Hematology.
CITATION STYLE
Kimura, H., Ishibashi, T., Shikama, Y., Okano, A., Akiyama, Y., Uchida, T., & Maruyama, Y. (1990). Interleukin-1β (IL-1β) induces thrombocytosis in mice: Possible implication of IL-6. Blood, 76(12), 2493–2500.
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