title: Cytokine changes in response to TPO receptor agonist treatment in primary immune thrombocytopenia.
abstract: Thrombopoietin receptor agonists (TPO-RAs) have been clinically used in primary immune thrombocytopenia (ITP) with favorable outcomes, while their effect on cytokine regulation in ITP remains unknown. In the present study, plasma and mRNA expression levels of interleukin (IL)-2, interferon gamma (IFN-γ), IL-4, IL-17A, and transforming growth factor-β1 (TGF-β1) were determined by ELISA and real-time quantitative PCR in 26 corticosteroid-resistant/relapsed ITP patients receiving eltrombopag or rhTPO therapy and 15 healthy controls (HCs). Results showed that plasma and mRNA levels of IL-2, IFN-γ, IL-4, and IL-17A in ITP patients did not change significantly after TPO-RA treatment, whereas TGF-β1 levels increased remarkably. The pre- and post-treatment plasma and mRNA levels of IFN-γ and IL-2 were significantly higher, while the pre- and post-treatment IL-4 levels as well as the pre-treatment TGF-β1 levels were remarkably lower in ITP patients compared with HCs. There was no significant difference in TGF-β1 levels between TPO-RA-treated ITP patients and HCs. No statistical difference was found in plasma levels of IL-17A between ITP patients before or after treatment and HCs. However, the pre- and post-treatment mRNA expression of IL-17A and retinoic orphan receptor (ROR) γt in ITP patients were higher than that in HCs. Overall, these findings indicated that TPO-RA treatment could promote the secretion of TGF-β1, while it could not correct the Th1 and Th17 polarization in ITP patients. This study might improve our understanding of the mechanism of action of TPO-RAs and provide important information for optimizing therapeutic strategies for ITP.
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Qu
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Xue-Na
authors.initials: XN
authors.lastname: Liu
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China. Electronic address: Liuxingrant@163.com.
authors.forename: Xin-Guang
authors.initials: XG
authors.lastname: Liu
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China; Department of Hematology, Taian Central Hospital, Taian, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Li
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhu
authors.affiliation: Reproductive Center, Rizhao Maternal & Child Health Hospital, Rizhao, PR China.
authors.forename: Ming-Yun
authors.initials: MY
authors.lastname: Lv
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China. Electronic address: qlhouming@sina.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000008:administration & dosage*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000097:blood; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism; D013926:Thrombopoietin / Q000008:administration & dosage*
chemical_list: D001565:Benzoates; D016207:Cytokines; D006834:Hydrazines; D011720:Pyrazoles; D012333:RNA, Messenger; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin; C520809:eltrombopag
keywords: Cytokines; Primary immune thrombocytopenia; T helper cells; Thrombopoietin receptor agonists