Effect of recombinant human interleukin‐11 on rat megakaryopoiesis and thrombopoiesis <i>in vivo:</i> comparative study with interleukin‐6

Yonemura, Yuji; Kawakita, Makoto; Masuda, Tetsuya; Fujimoto, Kouji; Takatsuki, Kiyoshi

doi:10.1111/j.1365-2141.1993.tb03020.x

Cited by 61 publications

(22 citation statements)

References 24 publications

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“…(6)(7)(8)(9) It has also proved to be an effective treatment for thrombocytopenia in patients who have undergone myelosuppressive chemotherapy. IL-11 also has a number of known biologic activities, (10)(11)(12)(13)(14)(15)(16) including roles in hematopoiesis and immune response and in the nervous system and bone metabolism.…”

Section: Introductionmentioning

confidence: 98%

Interleukin-11 Induces Osteoblast Differentiation and Acts Synergistically with Bone Morphogenetic Protein-2 in C3H10T1/2 Cells

Suga¹,

Saitoh²,

Fukushima³

et al. 2001

Journal of Interferon & Cytokine Research

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Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.

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Section: Introductionmentioning

confidence: 98%

Interleukin-11 Induces Osteoblast Differentiation and Acts Synergistically with Bone Morphogenetic Protein-2 in C3H10T1/2 Cells

Suga¹,

Saitoh²,

Fukushima³

et al. 2001

Journal of Interferon & Cytokine Research

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“…It has been reported that IL-11 also potentiates human and murine megakaryocyte development in vitro and acts synergistically with IL-3 to shorten the G0 period of early progenitors in both murine and human systems [11][12][13]. In vivo, IL-11 induces an increase in platelet counts and in the ploidy level of bone marrow megakaryocytes [14]. Administration of IL-11 to mice pretreated with cyclophosphamide decreased the time required to regain normal levels of platelet counts in peripheral blood [15].…”

Section: Il-11mentioning

confidence: 99%

Regulation of Megakaryocytopoiesis

Caen

Han²,

Bellucci³

et al. 1999

Pathophysiol Haemos Thromb

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After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use in a wide variety of clinical megakaryocytic and platelet disorders has been expected and clinical trials have been undertaken. To date, the reported encouraging pre-clinical studies indicate that, as with erythropoietin or G-CSF, minimal toxicity can be expected. A potential limiting side-effect of TPO could be the induction of thrombosis. Nevertheless, it is too early to know whether this cytokine will be of major therapeutic importance for patients with life-threatening thrombocytopenia, such as patients undergoing bone marrow transplantation or subjected to a high dose of chemotherapy. Several experimental and clinical studies are still needed to determine the efficacy of TPO in the prevention or the amelioration of bleeding, which is the ultimate goal for the appropriate use of cytokines with haemostatic benefit. Basic and clinical studies on regulators of megakaryocytopoiesis have rapidly progressed. Now, there is no doubt that some of these regulators are effective in correcting haematopoietic disorders of various aetiologies. Studies on negative regulators not only are important to understand the regulation of megakaryocytopoiesis in normal and pathological states but also have a potential clinical application. Some of these regulators have been shown to be effective in the treatment of essential thrombocythaemia and other myeloproliferative disorders. Platelet factor 4 (PF4) and some other chemokines are also capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs. However, detailed investigations are still required to determine the precise mechanism(s) of action of these regulators and to establish the optimal clinical protocols of negative regulators alone or in association with positive regulators for the treatment of various haematological diseases and cancer.

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“…IL-11 promotes the maturation of megakaryocytes in vitro (Bruno et al, 1991;Burstein et al, 1992;Teramura et al, 1992;Yonemura et al, 1992) and increases peripheral platelets in myelosuppressed animals (Neben et al, 1993;Yonemura et al, 1993;Nash et al, 1995;Schlerman et al, 1996). IL-11 induces osteoblast differentiation and acts synergistically with BMP-2 in C3H10T1/2 cells (Suga et al, 2001).…”

Section: Discussionmentioning

confidence: 95%