Background: Alveolitis and secondary lung fibrosis strongly influence prognosis and quality of life in patients with systemic sclerosis (SSc). Cytokines in the BALF mediate different pathogenic mechanisms and could be potential targets for a specific therapy of SSc lung involvement. However, there are only few data analysing the BALF cytokine levels of SSc patients, their specificity for SSc, their correlation to lung function parameters, and their influence on further development of lung diseases.
Objectives: The aim of the present study was to identify key cytokines in the BALF of SSc patients and to compare the cytokine levels to those present in other inflammatory lung diseases such as sarcoidosis. Furthermore, cytokine levels were correlated with the type of alveolitis, with the presence of CMV reactivation, with lung function parameters present before BAL and one year later to determine their prognostic impact.
Methods: 32 BALFs from SSc patients (23 with proven alveolitis and 9 without alveolitis) as well as from 21 controls including 9 patients with sarcoidosis were analysed for their cytokine levels using a bioplex analysis for different cytokines. Patients with infections were excluded from the study. FVC and DLCOc-SB were performed before and about one year after the bronchoscopy. CMV reactivation was determined by an increased frequency of CMV+ alveolar cells and by positive PCR.
Results: Basal BALF cytokine levels in patients without alveolitis do not differ in all investigated patients regardless of their associated disease. SSc patients with alveolitis show higher BALF IL-6 and MCP-1 levels compared to SSc patients without alveolitis. In contrast, alveolitis due to other diseases results in increased levels of GCSF, MIP1 and TNFalpha. Higher IL-7 and IL-8 levels and lower IL-6 levels in BALF are found in SSc patients with and without alveolitis compared to controls. SSc patients with lung fibrosis reveal higher levels of MCP-1 in comparison to patients without lung fibrosis. Controls with alveolitis (primary lung fibrosis, sarcoidosis) present higher BALF levels of IL-6 and lower levels of IL-7 compared to the SSc patients. In comparison to patients with alveolitis due to sarcoidosis, patients with SSc show increased levels of IL-6, IL-8, and MCP-1. In SSc patients, elevated IL-6 levels are associated with an increase in granulocytes in BAL. CMV reactivation (n = 4) is associated with increased levels of MCP-1 in SSc patients, but with increased levels of IL-4 in controls. Higher levels of MCP-1 and MIP1 are found in patients with a decrease in DLCO during one year follow-up in comparison to patients with stable DLCO. Patients with an improvement of FVC due to cyclophosphamide treatment show lower levels of IL-1, IL-6, IL-8, and GCSF compared to those with stable or decreased FVC.

Conclusion: In comparison to other diseases, SSc patients present a specific cytokine pattern in BALF. The detection of high MCP-1 levels in patients with fibrosis and in patients with decreased DLCO after one year of treatment suggests a key function of this cytokine as potential therapeutic target in SSc lung involvement.
References: The abstract has been supported by the German Network of systemic sclerosis and by the BMBF Germany