Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia (ITP)

Platelets. 2017 Jul;28(5):478-483. doi: 10.1080/09537104.2016.1235691. Epub 2016 Nov 7.


Background: Thrombopoietin-receptor-agonists (TPO-RAs) increase platelet production in Immune Thrombocytopenia (ITP) by stimulating Mpl. The effect of TPO-RAs on inflammatory cytokine production in ITP patients has not been well investigated.

Methods: Plasma samples from 48 ITP patients treated with TPO-RAs (median age 50 years (inter-quartile range; IQR 20-69), median platelet counts 24 × 109/L (IQR 15-47 × 109/L), 28 females) and 16 healthy controls (nine females, median age 37 years, IQR 22-51 years) were collected before and during treatment, and analyzed for a panel of cytokines and chemokines by enzyme-linked immunosorbent assay and immuno-bead-based multiplex assay.

Results: Elevated levels of C-X-C motif chemokine 10 (CXCL10; p < 0.001) and osteoprotegerin (OPG; p < 0.05) were observed in pretreatment samples compared to controls; these levels decreased during 6 months of treatment. Pretreatment levels of transforming growth factor (TGF)-β were lower than in healthy controls and increased after 6 months of treatment (p < 0.05). Levels of sCD40L increased after 6 months of treatment (p < 0.05), but decreased thereafter to pretreatment values. The increase in TGF-β and sCD40L may reflect increased platelet turnover. Levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 did not change during treatment.

Conclusion: These findings suggest that treatment with TPO-RA creates a more balanced steady-state of immune activation.

Keywords: Chemokines; cytokines; primary immune thrombocytopenia; thrombopoietin-receptor agonists.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Platelets / metabolism*
  • CD40 Ligand / blood*
  • Child, Preschool
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Purpura, Thrombocytopenic, Idiopathic / blood*
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Receptors, Thrombopoietin*
  • Time Factors


  • Cytokines
  • Receptors, Thrombopoietin
  • MPL protein, human
  • CD40 Ligand