Effect of cyclophosphamide on cytokines in patients with primary Sjögren’s syndrome-associated interstitial lung disease in South China

Abstract

The objective of the study is to investigate the mechanisms of cyclophosphamide sequential therapy for patient with primary Sjögren's syndrome-associated interstitial lung disease (PSS-ILD). 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 obtained before and 3, 6, 12 and 24 months after the treatment. The TNF-α and TGF-β1 mRNA levels in peripheral blood were measured using reverse transcription polymerase chain reaction. Serum and BALF TNF-α, TGF-β1 and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay. The average levels of serum TNF-α (0.39 ± 0.22) and TGF-β1 (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-β1 (0.31 ± 0.18) level markedly decreased after 6 months of treatment (t = 2.617, p < 0.05). The levels of serum TNF-α (11.2 ± 2.6) μg/L, TGF-β1 (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-β1 (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). The levels of BALF TNF-α (17.1 ± 3.5) μg/L, TGF-β1 (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-β1 (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 that may be associated with its inhabitation on production of TNF-α, TGF-β1 and MMP-9.

Risk factors for progression and prognosis of primary Sjögren’s syndrome‐associated interstitial lung disease in a Chinese population

“…In terms of treatment, this study showed that cyclophosphamide (CTX) can help to improve the progression of pSS‐ILD patients. A previous study 20 showed that the use of CTX in pSS‐ILD patients may inhibit tumor necrosis factor‐α, and then inhibit transforming growth factor‐β1 and matrix metalloproteinase‐9, and finally inhibit the progression of pulmonary fibrosis, which elucidated the effectiveness of CTX from the perspective of mechanism. Although CTX was not associated with survival in prognosis analysis, it was suggested that CTX can be considered as one of the effective drugs in the treatment of ILD in patients with pSS‐ILD.…”

Circulating Th2 cell reduction and Th1/Th2 imbalance are correlated with primary Sjogren’s syndrome-associated interstitial lung disease

“…In patients with diffuse lung parenchymal disease, T lymphocytes may express TGF-β in the lung tissue; TGF-β is an effective anti-inflammatory regulator and profibrotic cytokine [ 36 ]. Our previous study found that the serum level of TGF-β1, a key factor in the development of diffuse alveolar injury, alveolar endothelial cell necrosis and pulmonary fibrosis [ 37 , 38 ], was much higher in patients with ILD than in patients without ILD [ 32 ]. Thus, TGF-β-expressing T cells, particularly Th2 and Treg cells, may also be involved in the development of pulmonary fibrosis.…”

Chest HRCT findings in patients with primary Sjögren’s syndrome

“…In patients with active pSS, rituximab, belimumab and abatacept have also been used, but this treatment is uncommon due to its high cost, and questions relating to its usefulness in pSS still remain unanswered. [21][22][23][24] In conclusion, pulmonary involvement in pSS is common and occurs in around 30% of patients. This represents one of the most intriguing aspects of the disease.…”