Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis
Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis
复制标题
DOI：
10.1016/j.cyto.2012.08.032
复制
发表时间：
2013-01-01
期刊：
影响因子：
3.8
通讯作者：
Mimura, Yusuke
中科院分区：
文献类型：
--
作者：
Oishi, Keiji;Mimura-Kimura, Yuka;Mimura, Yusuke
特发性肺纤维化急性加重（AE-IPF）的特征是病因不明的呼吸困难严重恶化和未经有效治疗的高死亡率。最近，据报道，使用多粘菌素B（PMX）固定纤维药筒（PMX-DHP）直接血液灌流可改善AE-IPF患者的肺氧合和生存率，但其作用机制尚不清楚。为了通过PMX-DHP的有益作用深入了解AE-IPF的病理生物学，我们分析了9例AE-IPF患者中使用的PMX纤维上吸附的细胞因子谱。此外，还分析了在PMX-DHP之前和之后立即收集的这些AE-IPF患者、9名稳定IPF患者和8名健康个体的血清。PMX-DHP治疗后即刻血清IL-9、IL-12、IL-17、PDGF和VEGF水平均显著降低（P < 0.02），其中VEGF和IL-12降低最为显著。除了PDGF和VEGF之外，从使用的PMX纤维洗脱IL-1 β、IL-1 ra、IL-8、IL-23、碱性FGF、GM-CSF、IP-10、RANTES和TGF-β。有趣的是，PMX-DHP后改善的肺氧合与洗脱的VEGF的量很好地相关。这些结果表明，PMX纤维上促炎、促纤维化和促血管生成细胞因子的吸附是PMX-DHP在AE-IPF中的作用机制之一。值得注意的是，通过PMX-DHP去除VEGF可能有助于通过抑制肺中的血管通透性来快速改善氧合。(C)2012爱思唯尔有限公司保留所有权利。
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is characterized by severe worsening dyspnea of unknown etiology and high mortality without effective treatment. Recently, direct hemoperfusion with polymyxin B (PMX)-immobilized fiber cartridge (PMX-DHP) has been reported to improve pulmonary oxygenation and survival in patients with AE-IPF although its mechanism of action remains unknown. To gain insights into the pathobiology of AE-IPF through the beneficial effects of PMX-DHP, we analyzed the profile of cytokines adsorbed onto PMX-fibers used in 9 AE-IPF patients. In addition, the sera of these AE-IPF patients collected immediately before and after PMX-DHP, 9 stable IPF patients and 8 healthy individuals were also analyzed. The serum levels of cytokines including IL-9, IL-12, IL-17, PDGF and VEGF were significantly decreased immediately after PMX-DHP (P < 0.02), and VEGF and IL-12 were most prominently reduced. In addition to PDGF and VEGF, IL-1 beta, IL-1ra, IL-8, IL-23, FGF basic, GM-CSF, IP-10, RANTES and TGF-beta were eluted from used PMX-fibers. Interestingly, improved pulmonary oxygenation after PMX-DHP was correlated well with the quantities of eluted VEGF. These results suggest that adsorption of proinflammatory, profibrotic and proangiogenic cytokines onto PMX-fibers is one of the mechanisms of action of PMX-DHP in AE-IPF. Notably, removal of VEGF by PMX-DHP may contribute to the rapid improvement in oxygenation by suppressing vascular permeability in the lung. (C) 2012 Elsevier Ltd. All rights reserved.