title: Pulsed high-dose dexamethasone modulates Th1-/Th2-chemokine imbalance in immune thrombocytopenia.
abstract: Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways.
  
  
  
  Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied. Plasma levels of CCL5 and CXCL11 (Th1-associated) and of CCL11 (Th2-associated) were determined by ELISA. Gene expression of these three chemokines and their corresponding receptors CCR5, CXCR3, and CCR3, in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR.
  
  
  
  Thirty-three of the thirty-eight ITP patients responded effectively to HD-DXM (oral, 40 mg/day, 4 days). In ITP patients, plasma CXCL11 levels increased, while CCL11 and CCL5 decreased compared to controls (P < 0.05). Similarly, gene expression of CXCL11 and its receptor CXCR3 increased, while CCL11 and CCR3 decreased (P < 0.05). CCL5 expression did not significantly change; however, expression of its receptor CCR5 increased (P < 0.05). Interestingly, in the patients who responded to pulsed HD-DXM, CXCL11 and CXCR3 expression was down-regulated, while CCL11 and CCR3 expression was up-regulated (P < 0.05). Meanwhile, CCL5 expression was up-regulated and CCR5 was down-regulated by HD-DXM (P < 0.05).
  
  
  
  The abnormal profiles of Th1-/Th2-associated chemokines and chemokine receptors may play important roles in the pathogenesis of ITP. Importantly, regulating Th1 polarization by pulsed HD-DXM may represent a novel approach for immunoregulation in ITP.
authors: Medical College, Shandong University, Jinan, 250012, China.|Department of Hematology and Oncology, Tancheng Hospital, Linyi, 276100, China.
authors: Zongtang
authors: Z
authors: Liu
authors: Department of Rheumatology and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518000, China.
authors: Meiying
authors: M
authors: Wang
authors: Department of Rheumatology and Immunology, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, the 2nd Longjing Road, Baoan, Shenzhen, 518101, China.
authors: Shufen
authors: S
authors: Zhou
authors: Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors: Ji
authors: J
authors: Ma
authors: Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors: Yan
authors: Y
authors: Shi
authors: Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors: Jun
authors: J
authors: Peng
authors: Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors: Ming
authors: M
authors: Hou
authors: Department of Rheumatology and Immunology, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, the 2nd Longjing Road, Baoan, Shenzhen, 518101, China. guochengshan1@163.com.|Shenzhen Research Institute of Shandong University, Shenzhen, 518057, China. guochengshan1@163.com.|Department of Rheumatology, the Affiliated Shenzhen Baoan Hospital of Guangdong Medical University, Shenzhen, 518101, China. guochengshan1@163.com.
authors: Chengshan
authors: C
authors: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018925:Chemokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002648:Child; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D003907:Dexamethasone
keywords: Chemokine; Chemokine receptor; High-dose dexamethasone; Immune thrombocytopenia; Th1 polarization