1. Effects of Designer Hyper-Interleukin 11 (H11) on Hematopoiesis in Myelosuppressed Mice.
- Author
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Dams-Kozlowska H, Kwiatkowska-Borowczyk E, Gryska K, Lewandowska A, Marszalek A, Adamczyk S, Kowalik A, Leporowska E, and Mackiewicz A
- Subjects
- Animals, Bone Marrow drug effects, Bone Marrow immunology, Bone Marrow pathology, Colony-Forming Units Assay, Designer Drugs administration & dosage, Disease Models, Animal, Female, Hematopoiesis immunology, Hematopoietic Stem Cells drug effects, Hematopoietic Stem Cells immunology, Hematopoietic Stem Cells pathology, Interleukin-11 Receptor alpha Subunit administration & dosage, Mice, Mice, Inbred BALB C, Recombinant Fusion Proteins administration & dosage, Spleen drug effects, Spleen immunology, Spleen pathology, Thrombocytopenia pathology, Hematopoiesis drug effects, Interleukin-11 administration & dosage, Thrombocytopenia drug therapy
- Abstract
The incidence of cancer is constantly increasing. Chemo/radiotherapy is one of major methods of treating cancer. Although adverse chemo/radiotherapy events, such as anemia and neutropenia, can be successfully cured, thrombocytopenia is still problematic. We constructed the Hyper-IL11 (H11) cytokine by linking soluble interleukin 11 receptor alpha (sIL-11Ralpha) with IL-11. In vivo H11 activity was examined in myelosuppressed mice. Myelosuppression was induced by either i) sublethal irradiation and carboplatin administration or ii) sublethal irradiation. A dose of 100 μg/kg of H11 or IL-11 was administered subcutaneously for 7 days. IL-11 and H11 accelerated leukocyte, hematocrit and platelet recovery. The effect on the attenuation of thrombocytopenia was significant. Moreover, both cytokines increased the cellularity and numbers of megakaryocyte, erythroid, and granulocyte/macrophage progenitors in the bone morrow and spleen compared with the control. Although H11 was administered at a molar concentration that was three times lower, its effects were comparable with or better than those of IL-11; thus, the activity of H11 was superior to that of IL-11. Because no toxicity was observed after the intravenous administration of H11, this hyper-cytokine may be potentially useful for treatment of thrombocytopenia and other IL-11-dependent disorders.
- Published
- 2016
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