[环磷酰胺对原发性干燥综合征相关间质性肺疾病患者细胞因子的影响]

[The effect of cyclophosphamide on cytokines in patients with primary Sjögren's syndrome-associated interstitial lung disease].

作者信息

Mo Han-you, Wang Li-fang, Xu Jia, Shi Yu-hong, Yang Min, Zhou Run-hua

机构信息

Department of Rheumatology, the Affiliated Hospital of Guilin Medical College, Guilin, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2011 Jul;34(7):495-9.

PMID:22041773

Abstract

OBJECTIVE

To investigate the mechanisms of cyclophosphamide sequential therapy for patients with primary Sjögren's syndrome-associated interstitial lung disease (PSS-ILD).

METHODS

This was a retrospective review of 15 patients (2005 - 2008) with PSS-ILD who underwent cyclophosphamide sequential therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtain before and 3, 6, 12, 24 months after the treatment. The TNF-α and TGF-β(1)mRNA levels in peripheral blood were measured using reverse transcription-polymerase chain reaction (RT-PCR). Serum and BALF TNF-α, TGF-β(1)and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA).

RESULTS

(1) The average levels of serum TNF-α (0.39 ± 0.22) and TGF-β(1) (0.31 ± 0.18) mRNA in patients with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF-α level (0.23 ± 0.19) was significantly decreased 3 months after cyclophosphamide treatment (t = 2.533, P < 0.05), and TGF-β(1) (0.31 ± 0.18) level markedly decreased after 6 months of treatment (t = 2.617, P < 0.05). (2) The levels of serum TNF-α (11.2 ± 2.6) µg/L, TGF-β(1) (72 ± 19) µg/L and MMP-9 (38 ± 9) µg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β(1) (36 ± 12) µg/L level decreased significantly after 3 months of treatment (t = 2.526, P < 0.05), and TNF-α level (7.1 ± 1.3) µg/L markedly decreased after 6 months of therapy (t = 2.578, P < 0.05). MMP-9 level (18 ± 4) µg/L decreased significantly after 12-month treatment (t = 2.329, P < 0.05). (3) The levels of BALF TNF-α (17.1 ± 3.5) µg/L, TGF-β(1) (36 ± 17) µg/L and MMP-9 (27 ± 10) µg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β(1) (21 ± 14) µg/L level decreased significantly after 3-month treatment, and TNF-α level (9.4 ± 1.7) µg/L was decreased after 6 months of cyclophosphamide treatment (t = 2.215, P < 0.05). MMP-9 level (13 ± 5) µg/L decreased after 12 months of cyclophosphamide treatment (t = 2.576, P < 0.05).

CONCLUSION

The mechanisms of cyclophosphamide treatment may be associated with its inhibition on production of TNF-α, TGF-β(1)and MMP-9.

摘要

目的

探讨环磷酰胺序贯疗法治疗原发性干燥综合征相关间质性肺疾病（PSS-ILD）患者的机制。

方法

对15例（2005 - 2008年）接受环磷酰胺序贯疗法的PSS-ILD患者进行回顾性研究。在治疗前及治疗后3、6、12、24个月采集外周血和支气管肺泡灌洗（BALF）样本。采用逆转录-聚合酶链反应（RT-PCR）检测外周血中TNF-α和TGF-β(1)mRNA水平。采用夹心酶联免疫吸附测定（ELISA）检测血清和BALF中TNF-α、TGF-β(1)和MMP-9水平。

结果

（1）PSS-ILD患者血清TNF-α（0.39±0.22）和TGF-β(1)（0.31±0.18）mRNA平均水平高于无ILD的PSS患者。环磷酰胺治疗3个月后TNF-α水平（0.23±0.19）显著降低（t = 2.533，P < 0.05），治疗6个月后TGF-β(1)（0.31±0.18）水平明显降低（t = 2.617，P < 0.05）。（2）PSS-ILD患者血清TNF-α（11.2±2.6）μg/L、TGF-β(1)（72±19）μg/L和MMP-9（38±9）μg/L水平高于无ILD的PSS患者。治疗3个月后TGF-β(1)（36±12）μg/L水平显著降低（t = 2.526，P < 0.05），治疗6个月后TNF-α水平（7.1±1.3）μg/L明显降低（t = 2.578，P < 0.05）。治疗12个月后MMP-9水平（18±4）μg/L显著降低（t = 2.329，P < 0.05）。（3）PSS-ILD患者BALF中TNF-α（17.1±3.5）μg/L、TGF-β(1)（36±17）μg/L和MMP-9（27±10）μg/L水平高于无ILD的PSS患者。治疗3个月后TGF-β(1)（21±14）μg/L水平显著降低，环磷酰胺治疗6个月后TNF-α水平（9.4±1.7）μg/L降低（t = 2.215，P < 0.05）。环磷酰胺治疗12个月后MMP-9水平（13±5）μg/L降低（t = 2.576，P < 0.05）。