transforming-growth-factor-beta and Empyema--Pleural

Topics: Active Transport, Cell Nucleus; Adult; Aged; Aged, 80 and over; Animals; Bleomycin; Cell Nucleus; Disease Models, Animal; Empyema, Pleural; Female; Fibrosis; Humans; Male; Mice; Middle Aged; Myofibroblasts; Nuclear Proteins; Pleura; Soot; Trans-Activators; Transforming Growth Factor beta

We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid.. Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted.. We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-β was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001).. VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Topics: Adenosine Deaminase; Aged; Aged, 80 and over; Biomarkers; Diagnosis, Differential; Empyema, Pleural; Female; Heart Failure; Humans; Interleukin-8; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Male; Middle Aged; Pleural Effusion; Pleural Effusion, Malignant; Pneumonia; Predictive Value of Tests; Prospective Studies; Transforming Growth Factor beta; Tuberculosis; Vascular Endothelial Growth Factor A

Transforming growth factor (TGF)-beta is a cytokine that has been demonstrated to be an important modulator of inflammation and angiogenesis, as well as a potent stimulator of pleural fluid production and fibrosis. We previously demonstrated that rising levels of pleural fluid TGF-beta(1) correlate with pleural fibrosis in experimental empyema in rabbits. In this study, our hypothesis is that neutralization of TGF-beta with an intrapleural injection of a monoclonal antibody to TGF-beta will decrease pleural fibrosis in empyema.. Prospective, randomized, blinded study.. Animal research laboratory.. Nineteen rabbits.. An empyema was induced in 19 rabbits by intrapleural injection of Pasteurella multocida. A panspecific monoclonal antibody to TGF-beta was injected into the pleural space on 2 subsequent concurrent days in nine rabbits. Ten rabbits received intrapleural injections of bacteria alone and served as controls. All animals were then killed on day 6. Immunohistochemistry, using the antibody to TGF-beta, was performed on pleural tissue specimens from the control rabbits.. Immunohistochemistry revealed localization of TGF-beta to macrophages in the exudative material and the visceral pleura. After injection of the antibody to TGF-beta, the amount of purulent, exudative material in the pleural space of the nine experimental animals was markedly decreased at autopsy on day 6, relative to control animals. All markers of empyema and pleural fibrosis were also significantly decreased in the rabbits receiving intrapleural anti-TGF-beta.. TGF-beta localizes to macrophages in experimental empyema. Early intrapleural injection of an antibody to TGF-beta inhibits empyema formation and significantly decreases pleural fibrosis in experimental empyema.

Topics: Animals; Empyema, Pleural; Fibrosis; Injections, Intralesional; Male; Pleura; Pleural Diseases; Prospective Studies; Rabbits; Random Allocation; Transforming Growth Factor beta

Transforming growth factor-beta1 is an important immunomodulator. The diagnostic role of TGF-beta1 has not been systematically investigated in pleural effusion.. A prospective clinical study of 45 patients (23 men, 22 women; mean age 49 +/- 21 years) with pleural effusion was performed. Of these patients, 19 had malignant pleural effusion, 14 had tuberculous pleural effusion, seven had empyema/parapneumonic pleural effusion, and five had transudative pleural effusion due to congestive heart failure. The concentrations of TGF-beta1 were measured by ELISA in all pleural fluid samples and in serum samples only from patients with malignant and tuberculous pleural effusions.. The median TGF-beta1 levels of malignant, tuberculous and empyema/parapneumonic pleural effusions were 7.25 ng/mL, 7.81 ng/mL, and 9.75 ng/mL, respectively. There was no significant difference between them. The median TGF-beta1 level was 5.62 ng/mL in the transudate pleural effusion group and it was significantly lower than that in the empyema/parapneumonic group (P < 0.05). The pleural fluid TGF-beta1 levels did not correlate with cell profiles of the pleural fluid. The median serum TGF-beta1 levels in malignant and tuberculous pleural effusion groups were 7.38 ng/mL and 7.38 ng/mL, respectively. There was no significant difference between the levels of TGF-beta1 in paired samples of serum and pleural fluid.. This study shows that TGF-beta1 concentrations in exudative pleural effusions are higher than those in transudative effusions secondary to congestive heart failure but TGF-beta1 concentrations do not assist in differentiating exudative effusions.

Topics: Adult; Aged; Empyema, Pleural; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukocyte Count; Leukocytes, Mononuclear; Male; Middle Aged; Neutrophils; Pleural Effusion; Prospective Studies; Transforming Growth Factor beta

Malignant lymphoma frequently develops in the pleural cavity of the patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most of PALs are diffuse lymphoma of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses Epstein-Barr virus nuclear antigen 2 (EBNA2) that works as a target molecule for cell-mediated immune response. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF) beta 1 mRNA, however, neither expressed latent TGF beta binding protein (LTBP) mRNA at detectable level by Northern blot analysis. Because TGF beta expresses its functions in cooperation with LTBP, the biological functions of TGF beta 1 could be negligible. Neither cell lines expressed EBV BCRF1 mRNA at detectable level, a viral gene product which is partly homologous to human IL-10 and shares biological activities of IL-10. Since OPL-1 shows weaker proliferative activity than OPL-2 and expresses viral antigens, the production of an immunosuppressive cytokine, IL-10, might contribute to the development of overt lymphoma. The present study suggested that immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Topics: DNA, Viral; Empyema, Pleural; Epstein-Barr Virus Nuclear Antigens; Herpesvirus 4, Human; Humans; Immune Tolerance; Interleukin-10; Lymphoma, B-Cell; Pleural Neoplasms; Proliferating Cell Nuclear Antigen; Transcription, Genetic; Transforming Growth Factor beta; Tumor Cells, Cultured