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

Abstract

BackgroundChemokines 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.MethodsTh1-/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.ResultsThirty-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).ConclusionsThe 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.

CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia

“…Dexa was able to restore the inhibitory properties of ITP-MSCs on T-cells by reducing their viability. These data are in accordance with the well-identified primary role of GC in suppressing excessive T-cell [19] growth and in particular with the study of Buron et al, in which MSCs treated with Dexa are able to inhibit lymphocyte proliferation [33]. Interestingly, with CB 2 receptor stimulation we observed a more marked reduction of T-cell viability.…”

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

“…In ITP patients, plasma levels of CXCL11 are increased, as well as gene expression of CXCL11 in PBMCs [60]. In this work, it is hypothesized that CXCL11 is an important chemoattractant for effector T cells involved in ITP, and indeed, in patients who responded to pulsed high-dose dexamethasone, CXCL11 expression was down-regulated [60].…”

“…In this work, it is hypothesized that CXCL11 is an important chemoattractant for effector T cells involved in ITP, and indeed, in patients who responded to pulsed high-dose dexamethasone, CXCL11 expression was down-regulated [60]. CXCL2 is chemotactic for neutrophils and elevated expression of CXCL2 has also been associated with many inflammatory and autoimmune diseases [61, 62].…”

Immune regulation mechanism of vitamin�D level and IL‑17/IL‑17R pathway in Crohn's disease

“…This is also one of the immune regulation mechanisms of IL-17 (19,20). IL-12 is one of the most important regulators of Th0 cells differentiating into Th1 cells (21), and CXCL11 is a chemokine of Th1 cells (22). The results of this study showed that after 10 days of administration, model group of rats showed increased IL-17, IL-17R and Th17 levels in colon tissues, but showed significantly increased IL-12 and decreased CXCL11 levels when compared to control group.…”