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Effects of Designer Hyper-Interleukin 11 (H11) on Hematopoiesis in Myelosuppressed Mice.
- Source :
-
PloS one [PLoS One] 2016 May 04; Vol. 11 (5), pp. e0154520. Date of Electronic Publication: 2016 May 04 (Print Publication: 2016). - Publication Year :
- 2016
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27144685
- Full Text :
- https://doi.org/10.1371/journal.pone.0154520