Influence of inflammatory mechanisms on the redox balance in interstitial lung diseases

Abstract

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.

Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis

“…Using freshly isolated BAL cells, this study found no significant differences in TGF-b1 mRNA levels between patients and normal samples. However, increased transcripts levels of the anti-inflammatory cytokine IL-10 were noted, which is in line with other studies [4,6]. The data on TNF-a and IL-12p40 indicate that pulmonary cells other than BAL cells can produce and secrete these cytokines, as they differed significantly in patient and control BALF but not BAL cells.…”

“…As with previous studies on pulmonary sarcoidosis that demonstrated elevated expression of Th1 cytokines IL-2 and IFN-c, and showed little or no detectable expression of Th2 cytokines in BAL cells [3,24], these results are in line with a preferential Th1 cytokine expression at sites of disease in sarcoidosis. No significant changes in the transcript levels for TNF-a or IL-12p40 were found in BAL cells from sarcoidosis patients, which contrasted with some previous studies [24,25] but was in line with others [4,7,26,27]. Such discrepancies can depend on the choice of patient group, including smoking habits or previous/ongoing treatment, and the sensitivity of the methods.…”

“…An imbalance in the expression of T-helper cell type (Th)1/Th2 cytokines by alveolar cells has been suggested to be of importance for the outcome of a pulmonary immune response in sarcoidosis [2,3]. A number of studies on mRNA and protein levels of interleukin (IL)-2 and interferon (IFN)-c in the lungs [4][5][6] support the concept of sarcoidosis as a Th1-mediated disease. IL-12 acts as an important mediator of the Th1 polarisation in sarcoidosis [7].…”

Protein Oxidation by Chronic Pulmonary Diseases in Children

“…23,24 Our observations that neutrophils may play a leading role in pulmonary protein damage are in line with data showing that a low IL-10/IL-8 mRNA ratio is paralleled with significant oxidative stress in ILD. 25 Neutrophils play a central role in local pulmonary host defenses, and their persistence in the alveolar compartment may lead to excessive inflammation and oxidative damage. Eosinophils may play a similar role, but were unlikely to have contributed to protein oxidation in the children studied because eosinophils were rarely present in the BAL fluid.…”

Exhaled 8-isoprostane in sarcoidosis: relation to superoxide anion production by bronchoalveolar lavage cells

“…An example is idiopathic pulmonary fibrosis (IPF), a disease characterized by fatal prognosis due to massive lung fibrosis and unresponsiveness to treatment [1]. Increased ex-vivo production of superoxide anion or hydrogen peroxide by cells from bronchoalveolar lavage (BAL) have also been reported in sarcoidosis [2, 3], but secondary markers of oxidative stress, such as oxidized proteins, or oxidized methionine residues in BAL fluid (BALF) are not increased in sarcoidosis, contrary to IPF [4–6]. …”