Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible implication of IL-6.
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.
Kimura
H
H
First Department of Internal Medicine, Fukushima Medical College, Japan.
Ishibashi
T
T
Shikama
Y
Y
Okano
A
A
Akiyama
Y
Y
Uchida
T
T
Maruyama
Y
Y
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000009:adverse effects*; D007377:Interleukin-3 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D010976:Platelet Count / Q000187:drug effects; D012644:Selenium Radioisotopes; D012645:Selenomethionine / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013922:Thrombocytosis / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology
D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D012644:Selenium Radioisotopes; D004921:Erythropoietin; D012645:Selenomethionine