Pulsed high-dose dexamethasone modulates Th1-/Th2-chemokine imbalance in immune thrombocytopenia

• Published in: Journal of translational medicine Vol. 14; no. 1; p. 301
• Main Authors: Liu, Zongtang, Wang, Meiying, Zhou, Shufen, Ma, Ji, Shi, Yan, Peng, Jun, Hou, Ming, Guo, Chengshan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.10.2016; BioMed Central; BMC
• Subjects: Adolescent; Adult; Aged; Care and treatment; Chemokine; Chemokine receptor; Chemokines; Chemokines - blood; Chemokines - genetics; Chemokines - metabolism; Child; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Dosage and administration; Dose-Response Relationship, Drug; Female; Gene expression; Health aspects; High-dose dexamethasone; Humans; Immune thrombocytopenia; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic - blood; Purpura, Thrombocytopenic, Idiopathic - drug therapy; Purpura, Thrombocytopenic, Idiopathic - genetics; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 polarization; Th2 Cells - drug effects; Th2 Cells - immunology; Thrombocytopenia; Young Adult; China; Chemokine; Th1 polarization; Chemokine receptor; High-dose dexamethasone; Immune thrombocytopenia
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-016-1064-9

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.