Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible implication of IL-6

Abstract

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.

A combination of megakaryocyte growth and development factor and interleukin‐1 is sufficient to culture large numbers of megakaryocytic progenitors and megakaryocytes for transfusion purposes

“…The effects of IL-1 on platelet production could be partly indirect by its stimulating role in the formation of other cytokines. IL-1-induced production of IL-6 has been described both in humans (Brach et al, 1990;Jiang et al, 1994) and in mice (Kimura et al, 1990;Dan et al, 1995). In our culture system IL-6 production was observed if cells were cultured with PEGrHuMGDF and IL-1 (data not shown); this is in agreement with other papers in which IL-6 production by megakaryocytes was described (Jiang et al, 1994;Wickenhauser et al, 1995).…”

“…Several lines of evidence suggest a role for IL-1 in platelet production. In vivo administration of IL-1bb to humans treated with chemotherapy (Crown et al, 1991(Crown et al, , 1993Redman et al, 1994;Rinehart et al, 1997) and to mice (Kimura et al, 1990;Dan et al, 1995) resulted not only in an improved neutrophil recovery but also in thrombocytosis. In patients with rheumatoid arthritis with marked thrombocytosis, increased plasma IL-1bb levels were found (Ertenli et al, 1996).…”

Platelets fuel the inflammasome activation of innate immune cells

“…As both IL-1α and IL-1β induce thrombocytosis in mice (Kimura et al, 1990; Nishimura et al, 2015; Trinh et al, 2015), our findings raise the possibility that platelets could help feed an inflammatory loop by potentiating and sustaining IL-1 signaling, which in turn stimulates platelet biogenesis. However, whether thrombocytosis is a marker of disease or a contributor to pathogenesis, remains to be investigated.…”

Dose‐dependent structural and immunological changes in the placenta and fetal brain in response to systemic inflammation during pregnancy

“…IP injection of IL‐1β into timed‐pregnant mice for four consecutive days has been established as a model for studying the complications of sub‐chronic maternal inflammation 28‐35 . rIL‐1β dosing was determined based upon prior studies in which comparable doses of rIL‐1β caused a febrile response or thrombocytosis in mice 67,68 . In the context of our model, systemic rIL‐1β injection was performed to find the role of IL‐1β solely as a damaging factor in the setting of maternal sub‐chronic inflammation during pregnancy.…”