内源性血液中干扰素-γ的最大产量可能预测特发性肺纤维化患者对1β干扰素治疗的反应。

Endogenous blood maximal interferon-gamma production may predict response to interferon-gamma 1beta treatment in patients with idiopathic pulmonary fibrosis.

作者信息

Luppi F, Losi M, D'Amico R, Fabbri L M, Richeldi L

机构信息

Center for Rare Lung Disease, University of Modena and Reggio Emilia, Italy.

出版信息

Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(1):64-8.

PMID:19960790

Abstract

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disorder with a mean survival of 3 years after diagnosis. Treatment with interferon-gamma (IFN-gamma) 1beta has been reported to significantly improve lung function and arterial oxygen saturation in a first randomized controlled trial; unexpectedly, these findings have not been confirmed in a subsequent large placebo-controlled randomized study. Another larger placebo-controlled randomized trial has been stopped because data analyzed at interim analysis excluded the possibility that treatment with IFN-gamma 1beta would cause a significant reduction in the risk of death.

METHODS

Seven Italian male patients diagnosed with IPF were treated with IFN-gamma 1beta (200 microg/die subcutaneously three times a week), accordingly to the indications of the Italian Drug Agency. Based on available studies the response to treatment was pre-defined as changes in either lung function (FVC and DLCO) or oxygen arterial saturation. All patients consented to provide a peripheral blood sample for endogenous IFN-gamma production measurement with the ELISpot assay before treatment and 6 months thereafter.

RESULTS

Four of 7 patients improved or stabilized their lung function after 6 months treatment. Using the ELISpot assay to quantify the maximal production of endogenous IFN-gamma on peripheral blood samples, these 4 patients had a significantly higher endogenous IFN-gamma production before therapy, as compared to the 3 patients who deteriorated (91.3 +/- 49.6 vs. 277.8 +/- 34.2 spot forming cells, p = 0.023). No significant differences were observed after 6 months of treatment.

DISCUSSION

These preliminary results suggest that some IPF patients might benefit from treatment with IFN-gamma 1beta and may help to interpret the results of large randomized trials, suggesting that individual susceptibility could determine clinical response to treatment.

摘要

背景

特发性肺纤维化（IPF）是一种无法治愈的肺部疾病，诊断后平均生存期为3年。在第一项随机对照试验中，据报道使用γ-干扰素（IFN-γ）1β治疗可显著改善肺功能和动脉血氧饱和度；出乎意料的是，这些发现并未在随后一项大型安慰剂对照随机研究中得到证实。另一项更大规模的安慰剂对照随机试验已停止，因为中期分析所分析的数据排除了使用IFN-γ 1β治疗会显著降低死亡风险的可能性。

方法

根据意大利药品管理局的指示，7名被诊断为IPF的意大利男性患者接受了IFN-γ 1β治疗（每周皮下注射3次，每次200微克）。根据现有研究，将治疗反应预先定义为肺功能（FVC和DLCO）或动脉血氧饱和度的变化。所有患者均同意在治疗前及治疗6个月后提供外周血样本，用于通过ELISpot检测法测量内源性IFN-γ的产生。

结果

7名患者中有4名在治疗6个月后肺功能得到改善或稳定。使用ELISpot检测法对外周血样本中内源性IFN-γ的最大产生量进行量化，与3名病情恶化的患者相比，这4名患者在治疗前内源性IFN-γ产生量显著更高（91.3±49.6对277.8±34.2个斑点形成细胞，p = 0.023）。治疗6个月后未观察到显著差异。