Effects of Designer Hyper-Interleukin 11 (H11) on Hematopoiesis in Myelosuppressed Mice

PLoS One. 2016 May 4;11(5):e0154520. doi: 10.1371/journal.pone.0154520. eCollection 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Colony-Forming Units Assay
  • Designer Drugs / administration & dosage
  • Disease Models, Animal
  • Female
  • Hematopoiesis / drug effects*
  • Hematopoiesis / immunology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / pathology
  • Interleukin-11 / administration & dosage*
  • 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 / drug therapy*
  • Thrombocytopenia / pathology

Substances

  • Designer Drugs
  • Interleukin-11
  • Interleukin-11 Receptor alpha Subunit
  • Recombinant Fusion Proteins

Grants and funding

The study was supported by a grant from The National Science Centre, Poland (2011/01/B/NZ4/05796). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.