title: Effects of Designer Hyper-Interleukin 11 (H11) on Hematopoiesis in Myelosuppressed Mice.
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.
authors.affiliation: Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland.|Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Dams-Kozlowska
authors.affiliation: Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland.|Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Kwiatkowska-Borowczyk
authors.affiliation: Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gryska
authors.affiliation: Department of Oncologic Pathology and Prophylactics, Poznan University of Medical Sciences, Poznan, Poland.|Department of Oncologic Pathology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lewandowska
authors.affiliation: Department of Oncologic Pathology and Prophylactics, Poznan University of Medical Sciences, Poznan, Poland.|Department of Oncologic Pathology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszalek
authors.affiliation: Department of Medical Physics, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Adamczyk
authors.affiliation: Department of Medical Physics, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalik
authors.affiliation: Department of Laboratory Diagnostics, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Leporowska
authors.affiliation: Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland.|Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003114:Colony-Forming Units Assay; D015198:Designer Drugs / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017370:Interleukin-11 / Q000008:administration & dosage*; D053703:Interleukin-11 Receptor alpha Subunit / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D015198:Designer Drugs; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins