title: [The effect of cyclophosphamide on cytokines in patients with primary Sjögren's syndrome-associated interstitial lung disease].
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).
  
  
  CONCLUSIONS
  The mechanisms of cyclophosphamide treatment may be associated with its inhibition on production of TNF-α, TGF-β(1)and MMP-9.
authors: Department of Rheumatology, the Affiliated Hospital of Guilin Medical College, Guilin, China. mohanyou@sohu.com
authors: Han-you
authors: HY
authors: Mo
authors: Li-fang
authors: LF
authors: Wang
authors: Jia
authors: J
authors: Xu
authors: Yu-hong
authors: YH
authors: Shi
authors: Min
authors: M
authors: Yang
authors: Run-hua
authors: RH
authors: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D012189:Retrospective Studies; D012859:Sjogren's Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; D020780:Matrix Metalloproteinase 9