We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.

Obliterative bronchiolitis (OB) is the major long-term complication following lung and heart-lung transplantation. In bronchoalveolar lavage fluid samples obtained from patients suffering from OB, a marked increase in the number of neutrophils and elevated expression of transforming growth factor (TGF)-b 1 had been found. The goal of the study was to evaluate whether TGF-b 1 is capable of interfering with the expression of the secretory leukoprotease inhibitor (SLPI), the dominating defence of the conducting airways against neutrophil elastase (NE).The authors analysed the effects of TGF-b 1 on gene expression and protein release of SLPI by cultured human bronchial epithelial (BEAS-2B) cells. SLPI protein levels in the supernatants were quantified with a specific enzyme-linked immunosorbent assay; SLPI messenger ribonucleic acid (mRNA) levels were measured by reverse transcriptase polymerase chain reaction.Incubation with TGF-b 1 induced a marked decrease in SLPI protein levels (1 ng . mL and NE also caused a significant reduction in SLPI synthesis (10 ng . mL -1 TGF-b 1 + 7.5 U . mL -1 NE: mRNA SI = 0.61, p<0.05; protein SI = 0.65, p<0.05; 50 ng . mL -1 TGF-b 1 + 7.5 U . mL -1 NE: mRNA SI = 0.52, p<0.05; protein SI = 0.58, p<0.05; 10 ng . mL -1 TGF-b 1 : mRNA SI = 0.33, p<0.01; protein SI = 0.38, p<0.01). In conclusion, the data suggest that the coincidence of neutrophilia and upregulation of transforming growth factor-b 1 in obliterative bronchiolitis may lead to uninhibited neutrophil elastase activity by downregulation of secretory leukoprotease inhibitor, with the consequence of ongoing injury to the epithelium. Eur Respir J 2000; 15: 1052±1057.