FIZZ1和白细胞介素4及γ-干扰素在弥漫性间质性肺疾病中的表达及对患者临床转归的影响

Expressions of found in inflammatory zone 1,interleukin-4 and γ-interferon in diffuse interstitial lung disease and the effect on clinical outcomes

目的探讨FIZZ1、白细胞介素4(IL-4)、γ-干扰素在弥漫性间质性肺疾病(DILD)中的表达及对患者临床转归的影响。方法前瞻性选取2011年1—12月于重庆医科大学附属大学城医院首次确诊为DILD的患者37例,分别于治疗前、治疗3个月后检测患者肺组织中FIZZ1蛋白、FIZZ1 mRNA及肺泡灌洗液中白细胞介素4(IL-4)和γ-干扰素的表达情况,并根据患者的疾病转归将其分为治疗有效组和治疗无效组。结果治疗3个月后27例有效(治疗有效组),10例无效(治疗无效组)。治疗后,治疗有效组肺组织中FIZZ1蛋白、FIZZ1 mRNA和肺泡灌洗液中IL-4水平明显低于治疗无效组[(0. 49±0. 12)比(0. 71±0. 18)、(0. 68±0. 19)比(0. 92±0. 23)、(45±8) ng/L比(105±9) ng/L],γ-干扰素水平明显高于治疗无效组[(28±5) ng/L比(15±3) ng/L](均P <0. 05)。治疗前患者FIZZ1蛋白、FIZZ1 mRNA与IL-4均呈正相关(r=0. 637,P <0. 001; r=0. 624,P <0. 001),与γ-干扰素均呈负相关(r=-0. 529,P <0. 001; r=-0. 511,P <0. 001)。结论 FIZZ1、IL-4、γ-干扰素在DILD中均有表达,且彼此存在相互作用。不同疾病转归患者的3种因子表达水平存在差异,通过探索有效方法抑制或调控其表达,将有效抑制早期肺纤维化形成,阻止肺功能减退,提高患者生活质量,同时为疾病转归、预后监测提供新的生物学标志物。

Objective To explore the expressions of found in inflammatory zone 1(FIZZ1),interleukin-4(IL-4)andγ-interferon(γ-IFN)in diffuse interstitial lung disease(DILD)and the effect on clinical outcomes.Methods A total of 37 patients diagnosed of DILD in University-Town Hospital of Chongqing Medical University from January to December 2011 were prospectively enrolled.Expressions of FIZZ1 protein and FIZZ1 mRNA in lung tissue,expressions of IL-4 andγ-IFN in bronchoalveolar lavage fluid were detected before and 3 months after treatment.The patients were divided into effective group and ineffective group according to the clinical outcomes.Results All patients were followed up for 3 months;27 cases were improved(effective group)and 10 cases were ineffective(ineffective group).After treatment,expression levels of FIZZ1 protein,FIZZ1 mRNA and IL-4 in the effective group were significantly lower than those in the ineffective group[(0.49±0.12)vs(0.71±0.18),(0.68±0.19)vs(0.92±0.23),(45±8)ng/L vs(105±9)ng/L];expression level ofγ-IFN in the effective group was significantly higher than that in the ineffective group[(28±5)ng/L vs(15±3)ng/L](P<0.05).Before treatment,FIZZ1 protein and mRNA expressions were positively correlated with IL-4 level(r=0.637,P<0.001;r=0.624,P<0.001)and they were negatively correlated withγ-IFN level(r=-0.529,P<0.001;r=-0.511,P<0.001).Conclusions There an interaction among expressions of FIZZ1,IL-4 andγ-IFN in patients with DILD and the expression levels are associated with clinical outcomes.Down-regulation of FIZZ1,IL-4,γ-IFN can inhibit early pulmonary fibrosis,restrain pulmonary dysfunction,improve quality of life;these factors may be new biomarkers for prognostic prediction of DILD.