Abstract

The pathophysiology of pulmonary fibrosis in patients with systemic sclerosis (SSc) is poorly understood, but a number of recent studies have demonstrated an inflammatory process involving the lower respiratory tract. The objective of the present study was to determine the concentrations of several cytokines in the bronchoalveolar lavage (BAL) fluid of patients with SSc and to assess whether the enhanced expression of certain cytokines is associated with the presence of alveolitis. BAL was performed on patients with SSc (with or without alveolitis) and on normal control subjects. Lyophilized BAL fluid samples were assayed by enzyme-linked immunosorbent assay for tumor necrosis factor alpha (TNF alpha), interleukin-1alpha (IL-1alpha), IL-4, IL-6, IL-8, macrophage inflammatory protein 1alpha (MIP-1alpha), and RANTES. There were significant differences between groups in the BAL fluid concentrations of TNF alpha (P = 0.0005, with levels in SSc patients with alveolitis higher than those in normal controls), IL-8 (P = 0.006, with levels in both SSc groups higher than those in normal controls), MIP-1alpha (P = 0.009, with levels in SSc patients with alveolitis higher than those in SSc patients without alveolitis and than those in normal controls), and RANTES (P = 0.03, with levels in SSc patients without alveolitis higher than those in normal controls). With the exception of RANTES, the highest levels were detected in SSc patients with alveolitis. Each of these cytokines, either alone or in combination, may play an important role in the pathogenesis of pulmonary fibrosis in SSc.

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