CD(8+ )T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

BACKGROUND: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD(8+ )TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD(3+), CD(4+ )and CD(8+)) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. METHODS: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD(68 )for macrophages, anti-elastase for neutrophils, and anti-CD(3), anti-CD(4), anti-CD(8 )for CD(3+)TLs, CD(4+)TLs, and CD(8+)TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV(1), FVC, TLC, DLCO, PaO(2), PaCO(2 )and P(A-a)O(2))] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. RESULTS: Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD(68+ )cells for the 16.6% ± 2, CD(3+ )TLs for the 28.8% ± 7, CD(4+ )TLs for the 14.5 ± 4 and CD(8+ )TLs for the 13.8 ± 4. CD(8+)TLs correlated inversely with FVC % predicted (r(s )= -0.67, p = 0.01), TLC % predicted (r(s )= -0.68, p = 0.01), DLCO % predicted (r(s )= -0.61, p = 0.04), and PaO(2 )(r(s )= -0.60, p = 0.04). Positive correlations were found between CD(8+)TLs and P(A-a)O(2 )(r(s )= 0.65, p = 0.02) and CD(8+)TLs and MRC score (r(s )= 0.63, p = 0.02). Additionally, CD(68+ )cells presented negative correlations with both FVC % predicted (r(s )= -0.80, p = 0.002) and FEV(1 )% predicted (r(s )= -0.68, p = 0.01). CONCLUSION: In UIP/IPF tissue infiltrating mononuclear cells and especially CD(8+ )TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis

Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance

<p>Abstract</p> <p>Background</p> <p>Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant and Th1/Th2 balances may play an important role in many of the processes of inflammation and fibrosis. The transcription factor Nrf2 acts as a critical regulator for various inflammatory and immune responses by controlling oxidative stress. We therefore investigated the protective role of Nrf2 against the development of pulmonary fibrosis.</p> <p>Methods</p> <p>To generate pulmonary fibrosis, both wild-type C57BL/6 mice and Nrf2-deficient mice of the same background were administered bleomycin intratracheally.</p> <p>Results</p> <p>The survival of Nrf2-deficient mice after bleomycin administration was significantly lower than that of wild-type mice. The degree of bleomycin-induced initial pulmonary inflammation and pulmonary fibrosis was much more severe in Nrf2-deficient mice than in wild-type mice. The expression of antioxidant enzymes and phase II detoxifying enzymes was significantly reduced in the lungs of Nrf2-deficient mice, concomitant with an elevation of lung 8-isoprostane level, compared with wild-type mice. The expression of Th2 cytokines, such as interleukin-4 and interleukin-13, was significantly elevated in the lungs of Nrf2-deficient mice with an increase in the number of Th2 cells that express GATA-binding protein 3.</p> <p>Conclusions</p> <p>The results indicated that Nrf2 protects against the development of pulmonary fibrosis by regulating the cellular redox level and lung Th1/Th2 balance. Thus, Nrf2 might be an important genetic factor in the determination of susceptibility to pulmonary fibrosis.</p

Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams