Influence of inflammatory mechanisms on the redox balance in interstitial lung diseases.
This study investigated the hypothesis that inflammatory, regulatory and antioxidant systems control the redox balance in interstitial lung diseases. Spontaneous mRNA expression of inflammatory cytokines and redox-active enzymes was examined in bronchoalveolar lavage (BAL) cells from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis (SARC) using RT-PCR analysis. Pulmonary oxidative stress was characterized by carbonyl-levels in the soluble BAL-fluid protein. Protein carbonyls were normal in SARC, but 2.4-fold increased in IPF. Here, the protein carbonyls correlated inversely with glutathione peroxidase mRNA. The message for IL-8 increased 14-fold in IPF and was accompanied by a marked influx of PMN, while these parameters were not altered in SARC. Levels of IL-10 transcripts increased in both diseases, but stronger in SARC (33-fold) than in IPF (22-fold), contributing to a high IL-10/IL-8 mRNA ratio in SARC (0.86) in comparison to IPF (0.07) and controls (0.04). In SARC but not in IPF, IFN-gamma mRNA was expressed at high levels and correlated inversely with the carbonyl levels. In both diseases, IL-1beta, TNF-alpha, and IL-6 mRNA transcripts remained at baseline level. In summary, a low IL-10/IL-8 mRNA ratio was paralleled with significant oxidative stress in IPF, while a high IL-10/IL-8 ratio and enhanced IFN-gamma expression went along with a physiological redox-balance in SARC.
GSF-National Research Centre for Environment and Health, Institute for Inhalation Biology, Ingolstaedter Landstr. 1, Neuherberg, München 85764, Germany. alenz@gsf.de
A G
AG
Lenz
H
H
Hinze-Heyn
A
A
Schneider
J
J
Behr
K
K
Häussinger
S
S
Heindi
F
F
Stanzel
K L
KL
Maier
D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D016207:Cytokines / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011506:Proteins / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism*
D000975:Antioxidants; D016207:Cytokines; D004798:Enzymes; D011506:Proteins; D012333:RNA, Messenger; D000429:Alcohol Oxidoreductases