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


CONCLUSIONS
These findings suggest that treatment with TPO-RA creates a more balanced steady-state of immune activation.
a Department of Haematology , Copenhagen University Hospital Roskilde , Denmark.|b Institute for Inflammation Research , Copenhagen University Hospital Rigshospitalet , Denmark.
Sif
S
Gudbrandsdottir
c Department of Medicine , Østfold Hospital Trust, and Institute of Clinical Medicine, Oslo University , Oslo , Norway.
Waleed
W
Ghanima
b Institute for Inflammation Research , Copenhagen University Hospital Rigshospitalet , Denmark.
Claus H
CH
Nielsen
d Haematology Branch, NHLBI , National Institutes of Health , Bethesda , MD , USA.
Xingmin
X
Feng
a Department of Haematology , Copenhagen University Hospital Roskilde , Denmark.
Hans C
HC
Hasselbalch
e Department of Paediatric Haematology/Oncology , Weill Cornell Medical College , New York , NY , USA.
James
J
Bussel
D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000097:blood*; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000188:drug therapy*; D053628:Receptors, Thrombopoietin; D013997:Time Factors
D016207:Cytokines; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D023201:CD40 Ligand
Chemokines; cytokines; primary immune thrombocytopenia; thrombopoietin-receptor agonists