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.