Different angiogenic CXC chemokine levels in bronchoalveolar lavage fluid after interferon gamma-1b therapy in idiopathic pulmonary fibrosis patients
Different angiogenic CXC chemokine levels in bronchoalveolar lavage fluid after interferon gamma-1b therapy in idiopathic pulmonary fibrosis patients
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DOI：
10.1016/j.pupt.2008.06.005
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发表时间：
2008-12-01
影响因子：
3.2
通讯作者：
Siafakas, Nikolaos M.
中科院分区：
文献类型：
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作者：
Antoniou, Katerina M.;Tzanakis, Nikolaos;Siafakas, Nikolaos M.
背景和目的：肺纤维化是一种毁灭性的疾病，治疗选择很少。导致异常血管重塑的血管生成受血管生成和血管生成抑制因子的相反平衡调节。本研究旨在评估三种血管生成因子在血管生成中的作用。（IL-8、ENA-78和GRO-α）和三种血管抑制剂干扰素γ-1b治疗前后支气管肺泡灌洗液（BALF）中的趋化因子（IFN，IP-10，ITAC）患者和方法：我们前瞻性地研究了20名患者（16名男性，4名女性），平均年龄为68岁（范围，40-75），患有组织学证实的IPF/UIP。患者接受IFN γ-1b 200 μ g皮下注射，每周3次。结果：IFN-γ-1b治疗12个月后，血管生成趋化因子水平显著下降（以pg/ml计的中值，IL-8/CXCL 8：640对比81，p < 0.05，ENA-78/CXCL 5：191对比51，p < 0.005和GRO-α：1827对比710，p < 0.005）。治疗后血管生成抑制趋化因子的水平未检测到显著差异（中位数，pg/ml，IP-10/CXCL 10：56 vs. 56.5，p = 0.6，ITAC/CXCL 11：43 vs. 47，p = 0.11）。然而，一个显着的减少，在IFN/CXCL 9：66与31，p = 0.006，已被检测到。结论：这些研究结果支持的概念，IFN γ可能是一个重要的介质调节血管生成平衡的IPF。然而，IFN γ-1b降低了IFN-γ水平，发现与IP-10和I-TAC水平无变化相关，可以部分解释该药物在IPF中的非有益作用。(C)2008年由Elsevier Ltd.出版
Background and aim: Pulmonary fibrosis is a devastating disease with few treatment options. Angiogenesis that leads to aberrant vascular remodeling is regulated by an opposing balance of angiogenic and angiostatic factors. The present study aims to evaluate the role of three angiogenic (IL-8, ENA-78 and GRO-a) and three angiostatic (MIG, IP-10, ITAC) chemokines in bronchoalveolar lavage fluid (BALF), before and after treatment with Interferon gamma-1b (IFN gamma-1b).Patients and methods: We studied prospectively 20 patients (16 males, 4 females) of median age 68 years (range, 40-75) with histologically confirmed IPF/UIP. Patients were assigned to receive IFN gamma-1b 200 mu g sc thrice a week. Angiogenic and angiostatic mediators' levels were measured by ELISA kits.Results: The levels of the angiogenic chemokines significantly decreased after 12 months (mo) of IFN-gamma-1b treatment (median values in pg/ml, IL-8/CXCL8: 640 vs. 81, p < 0.05, ENA-78/CXCL5: 191 vs. 51, p < 0.005 and GRO-alpha: 1827 vs. 710, p < 0.005). No significant differences were detected in the levels of the angiostatic chemokines after therapy (median values in pg/ml, IP-10/CXCL10: 56 vs. 56.5, p = 0.6, ITAC/CXCL11: 43 vs. 47, p = 0.11). However, a significant decrease in the MIG/CXCL9: 66 vs. 31, p = 0.006, has been detected.Conclusion: These findings support the notion that IFN gamma may be one of the important mediators regulating angiogenetic balance in IPF. However, IFN gamma-1b decreases MIG levels, finding that in association with no alteration in IP-10 and I-TAC levels, could explain in part the nonbeneficial effect of this drug in IPF. (C) 2008 Published by Elsevier Ltd.