Haematology Oncology Centre, Qilu Hospital, Shandong University, Jinan, China.
Haematologica. 2009 Nov;94(11):1603-7. doi: 10.3324/haematol.2009.007708. Epub 2009 Oct 1.
To evaluate the effects of high-dose dexamethasone (HD-DXM) on the balance of interleukin-18 (IL-18) and its endogenous antagonist IL-18 binding protein (IL-18BP) in ITP patients, IL-18, IL-18BP as well as IFN-gamma, IL-4 plasma levels and platelet counts were determined in 17 ITP patients receiving DXM 40 mg/day for four consecutive days and in 24 healthy subjects. Using RT-PCR, the mRNA expression of IL-18, IL-18BP, IFN-gamma, IL-4, T-box (T-bet) and GATA-binding protein 3(GATA-3) were studied in all subjects. The in vitro effects of DXM on IL-18BP and IL-18 of peripheral blood mononuclear cells (PBMCs) were studied by ELISA. HD-DXM administration increased IL-18BP and reduced IL-18 expression significantly (p<0.05), which resulted in a downregulation of IL-18/IL-18BP ratio p<0.05). In vitro, DXM had a significant effect on secretion of IL-18BP while diminishing IL-18 release from cultures of PBMCs. These results suggest that downregulation of IL-18/IL-18BP might account for its clinical efficacy of HD-DXM in active ITP.
为了评估大剂量地塞米松（HD-DXM）对 ITP 患者白细胞介素-18（IL-18）及其内源性拮抗剂 IL-18 结合蛋白（IL-18BP）平衡的影响，我们测定了 17 例接受 DXM 40mg/天连续 4 天治疗的 ITP 患者和 24 例健康受试者的 IL-18、IL-18BP 以及 IFN-γ、IL-4 血浆水平和血小板计数。通过 RT-PCR，研究了所有受试者的 IL-18、IL-18BP、IFN-γ、IL-4、T 框（T-bet）和 GATA 结合蛋白 3（GATA-3）的 mRNA 表达。通过 ELISA 研究了 DXM 对 PBMCs 中 IL-18BP 和 IL-18 的体外作用。HD-DXM 给药显著增加了 IL-18BP 并降低了 IL-18 的表达（p<0.05），导致 IL-18/IL-18BP 比值下调（p<0.05）。体外，DXM 对 IL-18BP 的分泌有显著影响，同时减少了 PBMCs 培养物中 IL-18 的释放。这些结果表明，下调 IL-18/IL-18BP 可能是 HD-DXM 在活动性 ITP 中临床疗效的原因。
