Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: Proinflammatory role of bronchial epithelial cells

Background, Obliterative bronchiolitis (OB), the most important long-term c omplication after lung transplantation, is thought to be a manifestation of chronic rejection within the airways, with the hallmarks inflammation and fibroproliferation. Methods. To characterize the inflammatory process in the context; of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL-10, and tran sforming growth factor (TGF)-beta on the protein and mRNA level in bronchoa lveolar lavage fluid samples obtained from patients with bronchiolitis obli terans syndrome (BOS) and without EOS, In addition, bronchial cells sampled by bronchial brushing were analyzed for mRNA expression. Results. In respiratory epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8 (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/-0.2 ng/ml ELF, P<0.005) were significantly el evated, In addition, bronchoalveolar lavage fluid cells of BOS patients sho wed increased expression of TGF-beta (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3-phosphate dehydrogenase [GAPDH], P=0.1 1) and IL-8 (0.25+/-0.13 vs, 0.09+/-0.03 O.D./O.D. GAPDH, P=0.53) without t he differences reaching statistical significance. In contrast, IL-8 mRNA ex pression of bronchial cells was significantly higher in the BOS group (0.85 +/-0.40 vs. 0.22+/-0.10 O.D./O.D. GAPDH, P<0.05). Conclusions. 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.