CD8+ T lymphocytes in bronchoalveolar lavage in idiopathic pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Recently it was shown that in Idiopathic Pulmonary Fibrosis (IPF) tissue infiltrating CD₈₊T lymphocytes (TLs) are associated with breathlessness and physiological indices of disease severity, as well as that CD₈₊TLs recovered by bronchoalveolar lavage (BAL) relate to those infiltrating lung tissue. Since BAL is a far less invasive technique than tissue biopsy to study mechanisms in IPF we further investigated the usefulness offered by this means by studying the relationship between BAL macrophages, neutrophils, eosinophils, CD₃₊, CD₄₊, CD₈₊, CD_8+/38+TLs and CD₄₊/CD₈₊ratio with breathlessness and physiological indices.</p> <p>Patients and methods</p> <p>27 IPF patients, 63 ± 9 years of age were examined. Cell counts were expressed as percentages of total cells and TLs were evaluated by flow cytometry. FEV₁, FVC, TLC, RV, <it>D</it>LCO, PaO₂, and PaCO₂were measured in all. Breathlessness was assessed by the Medical Research Council (MRC) chronic dyspnoea scale.</p> <p>Results</p> <p>CD₈₊TLs correlated positively (r_s= 0.46, p = 0.02), while CD₄₊/CD₈₊ratio negatively (r_s= -0.54, p = 0.006) with the MRC grade. CD₈₊TLs correlated negatively with RV (r_s= -0.50, p = 0.017). CD_8+/38+TLs were negatively related to the FEV₁and FVC (r_s= -0.53, p = 0.03 and r_s= -0.59, p = 0.02, respectively). Neutrophils correlated positively with the MRC grade (r_s= 0.42, p = 0.03), and negatively with the <it>D</it>LCO (r_s= -0.54, p = 0.005), PaO₂(r_s= -0.44, p = 0.03), and PaCO₂(r_s= -0.52, p = 0.01).</p> <p>Conclusion</p> <p>BAL CD₈₊TLs associations with physiological and clinical indices seem to indicate their implication in IPF pathogenesis, confirming our previous tissue study.</p

Specific effects of bortezomib against experimental malignant pleural effusion: a preclinical study

BACKGROUND: We have previously shown that nuclear factor (NF)-κB activation of mouse Lewis lung carcinoma (LLC) specifically promotes the induction of malignant pleural effusions (MPE) by these cells. In the present studies we hypothesized that treatment of immunocompetent mice with bortezomib tailored to inhibit cancer cell NF-κB activation and not proliferation specifically inhibits MPE formation by LLC cells. RESULTS: Treatment of LLC cells with low concentrations of bortezomib (100 ng/ml) inhibited NF-κB activation and NF-κB-dependent transcription, but not cellular proliferation. Bortezomib treatment of immunocompetent C57BL/6 mice bearing LLC-induced subcutaneous tumors and MPEs significantly blocked tumor-specific NF-κB activation. However, bortezomib treatment did not impair subcutaneous LLC tumor growth, but was effective in limiting LLC-induced MPE. This specific effect was evidenced by significant reductions in effusion accumulation and the associated mortality and was observed with both preventive (beginning before MPE formation) and therapeutic (beginning after MPE establishment) bortezomib treatment. The favorable impact of bortezomib on MPE was associated with suppression of cardinal MPE-associated phenomena, such as inflammation, vascular hyperpermeability, and angiogenesis. In this regard, therapeutic bortezomib treatment had identical favorable results on MPE compared with preventive treatment, indicating that the drug specifically counteracts effusion formation. CONCLUSIONS: These studies indicate that proteasome inhibition tailored to block NF-κB activation of lung adenocarcinoma specifically targets the effusion-inducing phenotype of this tumor. Although the drug has limited activity against advanced solid lung cancer, it may prove beneficial for patients with MPE

Interleukin-18 in induced sputum: Association with lung function in chronic obstructive pulmonary disease

SummaryBackgroundIt has been shown that interleukin (IL)-18 levels in induced sputum are reduced in asthmatic and healthy smokers. However, in chronic obstructive pulmonary disease (COPD) patients, recent data show an overproduction in the lungs and increased serum levels of IL-18, suggesting that IL-18 may be involved in the pathogenesis of COPD.MethodIn order to assess the relation of IL-18 with pulmonary function and airway inflammation in COPD, IL-18, tumour necrosis factor-α, and IL-8 levels were measured by ELISA in sputum supernatants obtained from patients with bronchitis type COPD (n=28), and healthy subjects (18 smokers and 17 non-smokers). Cellular localization of IL-18 was assessed by immunocytochemistry.ResultsThe levels of IL-18 were significantly higher in sputum supernatants of COPD patients compared to healthy smokers and non-smokers (p<0.05). IL-18 production was localized to sputum macrophages. IL-18 levels were inversely correlated with FEV1 (% predicted) (r=−0.572, p=0.002) and FEV1/FVC ratio in COPD smokers (r=−0.608, p=0.001). No correlations were found between IL-18 levels and inflammatory markers studied in induced sputum obtained from COPD patients, healthy smokers and non-smokers.ConclusionIn patients with COPD, increased levels of IL-18 in induced sputum were associated with airflow limitation, suggesting that IL-18 may be implicated in the pathogenesis of COPD

Interleukin-18 is up-regulated in infectious pleural effusions

The aim of this study was to investigate the pleural and systemic expression of interleukin-18 (IL-18) in patients with pleural effusions (PEs), and the effects of the cytokine in mouse pleural space. One hundred and sixty patients, 23 with pleural effusions (PEs) due to heart failure, 60 malignant, 25 parapneumonic/empyemas, 15 tuberculous and 37 with exudates of miscellaneous etiologies were included in the study. Pleural fluid (PF) and serum IL-18 content was determined using ELISA. IL-18 was injected intrapleurally in mice and pleural inflammation was assessed using pleural lavage. The highest PF IL-18 levels were observed in parapneumonic PEs and the lowest PF IL-18 levels in patients with exudates of miscellaneous aetiologies and transudates. PF IL-18 levels were significantly higher in patients with empyemas compared to those with uncomplicated (p = 0.009) or complicated (p = 0.028) parapneumonic effusions, while serum levels did not differ significantly among the three groups. Pleural IL-18 content was higher than that of blood only in patients with empyemas. In patients with pleural exudates of all etiologies and in those with parapneumonic PEs/empyema, PF IL-18 levels were correlated with markers of acute pleural inflammation such as the percentage of PF neutrophils, PF LDH and PF/serum LDH ratio, low PF glucose and PF/serum glucose ratio and low PF pH. In mice, intrapleural IL-18 caused neutrophil-predominant pleural inflammation. In conclusion, IL-18 is linked to the intensity of neutrophilic pleural inflammation in patients with PEs, it is up-regulated in the pleural space of patients with empyema and it stimulates the accumulation of neutrophils in mouse pleura. (c) 2013 The Authors. Published by Elsevier Ltd. All rights reserved