Tissue Localization of Transforming Growth Factor-β1 in Nonspecific Interstitial Pneumonitis Compared with Usual Interstitial Pneumonitis

Abstract

Idiopathic pulmonary fibrosis represents a heterogeneous group of disorders. Recent studies have identified clinical differences between patients with the more common usual interstitial pneumonitis (UIP) histologic pattern compared to the group classified with nonspecific interstitial pneumonitis (NSIP). Histologically, UIP is characterized by a heterogeneous pattern of normal lung, collagen fibrosis, and honeycomb changes. In many cases, active fibrotic lesions believed to result from organizing alveolar exudates are also present. In contrast, NSIP presents a more uniform pattern characterized by chronic interstitial pneumonia lacking features of other specific interstitial diseases. Prior studies have implicated a central role for transforming growth factor (TGF)-β1 in the pathogenesis of lung fibrosis. TGF-β1 mediates fibroblast proliferation and increases extracellular matrix deposition. Regional expression of TGF-β1 has been studied in UIP, but similar observations in NSIP are currently lacking. To address this, lung tissues from seven patients classified as having NSIP were evaluated in parallel with tissue obtained from eight patients with UIP. Sections were stained with a mouse monoclonal antibody recognizing human TGF-β1 (MAB1032; Chemicon International; Temecula, CA). The sections were blinded, coded, and evaluated randomly. The following patterns of TGF-β1 staining were observed. Lungs classified with UIP exhibited staining in loose and dense fibrous connective tissue strands in the interstitium and surrounding vessels and airways. Staining was also present in macrophage-rich inflammatory lesions and in fibrotic lesions consistent with organizing exudates. In contrast, lungs classified with NSIP showed a more uniform diffuse staining pattern localized to the thickened interstitial compartments and to accompanying inflammatory cells. In a semiquantitative manner, the overall intensity of TGF-β1 staining was also scored 1 + to 4 +. In these samples, tissues with UIP exhibited somewhat greater TGF-β1 staining compared to NSIP (TGF-β1 score of 3.4 ± 0.3 vs 2.6 ± 0.2; p = 0.04). These initial observations indicate differences in regional expression of TGF-β1 in patients with NSIP compared to those with UIP. Further studies will be required to determine the biological and clinical significance of these initial observations.