High-Dose Dexamethasone Alters the Increase in Interleukin-16 Level in Adult Immune Thrombocytopenia.

Qi Feng,Ming Hou,Jun Peng,Chengjiang Gao,Xin Li,Yuanjian Wang,Chunhong Ma,Xinru Wang,Yu Hou,Lizhen Li

doi:10.3389/fimmu.2019.00451

Abstract

Adult primary immune thrombocytopenia (ITP) is an autoimmune-mediated haemorrhagic disorder. Interleukin-16 (IL-16) can directly affect cellular or humoural immunity by mediating the cellular cross-talk among T cells, B cells and dendritic cells. Several studies have focused on IL-16 as an immunomodulatory cytokine that takes part in Th1 polarization in autoimmune diseases. In this study, we investigated IL-16 expression in the bone marrow supernatant and plasma of ITP patients and healthy controls. What's more, we detected IL-16 expression in ITP patients with the single-agent 4-day high-dose dexamethasone (HD-DXM) therapy. In patients with active ITP, bone marrow supernatant and plasma IL-16 levels increased (P < 0.05) compared with those of healthy controls. In the meantime, the mRNA expression in BMMCs (pro-IL-16, caspase-3) and PBMCs (pro-IL-16, caspase-3 and T-bet) of ITP patients was increased (P < 0.05) relative to those of healthy controls. In patients who responded to HD-DXM therapy, both plasma IL-16 levels and gene expression in PBMCs (pro-IL-16, caspase-3, and T-bet) were decreased (P < 0.05). In summary, the abnormal level of IL-16 plays important roles in the pathogenesis of ITP. Regulating Th1 polarization associated with IL-16 by HD-DXM therapy may provide a novel insight for immune modulation in ITP.

Highlights

Adult primary immune thrombocytopenia (ITP) is an autoimmune-mediated haemorrhagic disorder in which platelets are destroyed by specific antibodies directed against platelet surface membrane glycoproteins (GPs) and prematurely cleared by macrophages in the reticuloendothelial system [1]
N-IL-16 is located both in the cytolymph, as a substrate for mature IL-16 following expression of pro-IL16, caspase-3 in ITP patients with active disease and healthy controls in bone marrow mononuclear cells (BMMCs); ***P < 0.001; ** P < 0.01; * P < 0.05. (B) Relative mRNA expression of pro-IL16, caspase-3 and T-bet in peripheral blood mononuclear cells (PBMCs) in ITP patients with active disease and healthy controls. *** P < 0.001; ** P < 0.01; * P < 0.05. (C) mRNA expression of pro-IL16, caspase-3 and T-bet in active ITP before high-dose dexamethasone (HD-DXM), after HD-DXM and controls. *** P < 0.001; ** P < 0.01; * P < 0.05. (D) Correlation between plasma and mRNA expression levels of IL-16 in active ITP patients
Plasma IL-16 levels and pro-IL-16 mRNA expression in PBMCs were determined by enzyme-linked immunosorbent assay (ELISA) and real-time PCR

Summary

Introduction

Adult primary immune thrombocytopenia (ITP) is an autoimmune-mediated haemorrhagic disorder in which platelets are destroyed by specific antibodies directed against platelet surface membrane glycoproteins (GPs) and prematurely cleared by macrophages in the reticuloendothelial system [1]. The pathophysiology of ITP is characterized by excessive platelet destruction and a decrease in platelet production. Skewed balance of T helper cell type 1 (Th1) to T helper cell type 2 (Th2) [2, 3], reduced and defective capability of regulatory T cells [4, 5], abnormal Th17 and Th22 cells [6], cytotoxic T lymphocyte (CTL)–mediated platelet destruction [7], and altered levels of cytokines including IL-11, IL-18, IL-27, and IL-35 were involved in the pathogenesis of ITP [8,9,10,11]. There are several abnormalities contributing to the pathophysiology of ITP that remain to be explored.

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Conclusion