Eltrombopag in paediatric immune thrombocytopenia: Iron metabolism modulation in mesenchymal stromal cells

Br J Haematol. 2022 Apr;197(1):110-119. doi: 10.1111/bjh.18012. Epub 2021 Dec 28.

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease caused by platelet destruction mediated by auto-antibody production. It is characterized by a compromised immune system and alteration of the inflammatory response. Mesenchymal stromal cells (MSCs) play an important role in modulating immune and inflammatory processes, exerting immune-suppressing and anti-inflammatory properties. In ITP-MSCs the activity and survival are strongly impaired. Eltrombopag (ELT) is a thrombopoietin receptor agonist approved in chronic ITP for stimulating platelet production. It has immunomodulating properties by stimulating T and B regulatory cell activity and by promoting a macrophage switch from the pro-inflammatory to the anti-inflammatory phenotype. ELT also exhibits iron-chelating properties. Iron is a crucial element involved in several physiologic processes, but its intracellular accumulation determines cell damages. Therefore, for the first time we analysed the effect of ELT on ITP-MSCs demonstrating its ability to restore survival and activity of MSCs directly and to promote their survival and proliferation indirectly, by iron metabolism modulation.

Keywords: eltrombopag; immune thrombocytopenia; iron metabolism; mesenchymal stromal cells..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Benzoates / pharmacology
  • Benzoates / therapeutic use
  • Child
  • Humans
  • Hydrazines / pharmacology
  • Hydrazines / therapeutic use
  • Iron / therapeutic use
  • Mesenchymal Stem Cells*
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Pyrazoles
  • Thrombocytopenia* / drug therapy

Substances

  • Anti-Inflammatory Agents
  • Benzoates
  • Hydrazines
  • Pyrazoles
  • Iron
  • eltrombopag