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

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

Author information

1
a Department of Haematology , Copenhagen University Hospital Roskilde , Denmark.
2
b Institute for Inflammation Research , Copenhagen University Hospital Rigshospitalet , Denmark.
3
c Department of Medicine , Østfold Hospital Trust, and Institute of Clinical Medicine, Oslo University , Oslo , Norway.
4
d Haematology Branch, NHLBI , National Institutes of Health , Bethesda , MD , USA.
5
e Department of Paediatric Haematology/Oncology , Weill Cornell Medical College , New York , NY , USA.

Abstract

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

PMID:
27819522
DOI:
10.1080/09537104.2016.1235691
[Indexed for MEDLINE]

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