Strieter Robert M, Starko Karen M, Enelow Richard I, Noth Imre, Valentine Vincent G
David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90024-1922, USA.
Am J Respir Crit Care Med. 2004 Jul 15;170(2):133-40. doi: 10.1164/rccm.200312-1670OC. Epub 2004 Mar 24.
In a recent study of IFN-gamma 1b in 330 patients with idiopathic pulmonary fibrosis (IPF), progression-free survival was unchanged; however, a trend toward lower mortality was seen in IFN-gamma 1b-treated patients compared with placebo-treated patients (9.9 vs. 16.7%; p = 0.08). The purpose of this randomized, double-blind, placebo-controlled trial was to characterize molecular effects of subcutaneous IFN-gamma 1b (200 microg) thrice weekly for 6 months versus placebo in 32 patients with IPF. Messenger RNA in transbronchial lung biopsies and bronchoalveolar lavage cell pellet and protein levels in bronchoalveolar lavage fluid (BALF) and plasma were evaluated. After IFN-gamma 1b treatment, IFN-inducible T cell-alpha chemoattractant/CXCL11 (a chemokine with immunomodulatory, antiangiogenic, and defensin-like antimicrobial properties) increased in BALF (p = 0.016) and plasma (p < 0.001); BALF levels of epithelial neutrophil-activating protein-78/CXCL5 (p = 0.054), platelet-derived growth factor A (p = 0.033), and Type I procollagen (p = 0.096) were lower; and IFN-gamma levels were higher (p = 0.093) versus placebo. For messenger RNA in transbronchial biopsies, trends (p > 0.05 and <or= 0.10) associated with IFN-gamma 1b treatment included an increase in IFN-inducible T cell-alpha chemoattractant/CXCL11, a decrease in elastin, and smaller increases for Type III procollagen and platelet-derived growth factor B. Changes in biomarkers of fibrosis, angiogenesis, proliferation, immunomodulation, and antimicrobial activity suggest that IFN-gamma 1b may affect IPF through multiple pathways.
在一项近期针对330例特发性肺纤维化（IPF）患者开展的关于干扰素-γ1b的研究中，无进展生存期未发生改变；然而，与接受安慰剂治疗的患者相比，接受干扰素-γ1b治疗的患者死亡率有降低趋势（9.9% 对16.7%；p = 0.08）。本随机、双盲、安慰剂对照试验的目的是，对32例IPF患者皮下注射干扰素-γ1b（200微克）每周三次，共6个月与安慰剂相比的分子效应进行特征描述。评估经支气管肺活检组织、支气管肺泡灌洗细胞沉淀中的信使核糖核酸以及支气管肺泡灌洗液（BALF）和血浆中的蛋白质水平。接受干扰素-γ1b治疗后，BALF（p = 0.016）和血浆（p < 0.001）中的干扰素诱导T细胞α趋化因子/CXCL11（一种具有免疫调节、抗血管生成和防御素样抗菌特性的趋化因子）增加；BALF中上皮中性粒细胞激活蛋白-78/CXCL5（p = 0.054）、血小板衍生生长因子A（p = 0.033）和I型前胶原（p = 0.096）水平降低；与安慰剂相比，干扰素-γ水平升高（p = 0.093）。对于经支气管活检组织中的信使核糖核酸，与干扰素-γ1b治疗相关的趋势（p > 0.05且≤0.10）包括干扰素诱导T细胞α趋化因子/CXCL11增加、弹性蛋白减少，以及III型前胶原和血小板衍生生长因子B增加幅度较小。纤维化、血管生成、增殖、免疫调节和抗菌活性生物标志物的变化表明，干扰素-γ1b可能通过多种途径影响IPF。
