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. Munich Lung Transplant Group.
BACKGROUND
Obliterative bronchiolitis (OB), the most important long-term complication 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 transforming growth factor (TGF)-beta on the protein and mRNA level in bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis obliterans syndrome (BOS) and without BOS. 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 elevated. In addition, bronchoalveolar lavage fluid cells of BOS patients showed 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=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03 O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical significance. In contrast, IL-8 mRNA expression 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.
Department of Internal Medicine I, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. Elssner@med1.med.uni-muenchen.de
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A
Elssner
F
F
Jaumann
S
S
Dobmann
J
J
Behr
M
M
Schwaiblmair
H
H
Reichenspurner
H
H
Fürst
J
J
Briegel
C
C
Vogelmeier
D000328:Adult; D001989:Bronchiolitis Obliterans / Q000378:metabolism*; D001991:Bronchitis / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology; D016041:Heart-Lung Transplantation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta