Evidence for Chronic Inflammation as a Component of the Interstitial Lung Disease Associated with Progressive Systemic Sclerosis

Abstract

Progessive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs, including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS held it to be a pure fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis was associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, 67G scanning and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS was clearly associated with the presence of macrophages, lymphocytes and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. 67G scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least 1 mechanism modulating the lung fibrosis of these patients. Evidence from several different points of view together demonstrated that the interstitial lung disease associated with PSS was associated with chronic inflammation in the local milieu, leading to the hypothesis that the inflammation plays some role in the derangements to the alveolar structures that characterize this disorder. However, while this suggests a potential vulnerable site for therapy of this disorder, corticosteroids had no consistent effect on 67G scan or proportions of neutrophils and eosinophils in lavage fluid of these patients. While the interstitial lung disease associated with PSS is characterized by an alveolitis, the traditional therapy of interstitial lung disease does not suppress at least some components of this inflammation.