Expression Profiles of Cytokine mRNAs in the Pleural Fluid Reveal Differences Among Tuberculosis, Malignancies, and Pneumonia-Exudative Pleural Effusions

Our plain-English summary of Expression Profiles of Cytokine mRNAs in the Pleural Fluid Reveal Differences Among Tuberculosis, Malignancies, and Pneumonia-Exudative Pleural Effusions, by D.L. Espósito, V.R. Bollela, A.L. Feitosa, et al (Lung, 2015).

The study

• Authors: D.L. Espósito, V.R. Bollela, A.L. Feitosa, B.A. da Fonseca
• Journal: Lung
• Published: 2015;193(6):1001-7
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Tuberculosis (TB) and malignant diseases are the most common causes of lymphocytic pleural effusion in adults. Serum and pleural fluid cytokine levels have been analyzed to help in the differential diagnosis, but with limited results.

Purpose: This study investigates transcription levels of selected cytokine genes in pleural effusion of patients under investigation for TB.

Methods: This was a prospective study that included adult patients under investigation for pleural effusion in Brazil. The expression of 19 cytokine genes was analyzed by RT-qPCR.

Results: The majority of cytokine-related genes expressed in pleural fluid of TB patients were similar in non-TB patients, except for RORA and RORC genes, which showed a statistically higher level in TB. All cytokines in the Th17 pattern were induced in TB patients' pleural fluid. Patients with malignant pleural effusion expressed higher levels of IFN-α1, IFN-β1, TNF-α, IL-4 and IL-6, and suppression of TGFβ-1.

Conclusion: There is still a lot to understand about the cytokine roles in the pro- and anti-inflammatory environment of exudative pleural effusions. The data presented here showed an increased expression of Th17 pattern cytokines genes in TB patients that could be used as markers to differentiate tuberculous pleuritis from other common causes of exudative pleural effusion.

In plain English

This 12-month prospective study at a teaching hospital in southeast Brazil measured mRNA levels of 19 cytokine and transcription-factor genes in cells from fluid around the lungs of patients with exudative pleural effusions. Patients were meant to be over 18, but one analysed patient was listed as 12. Of 77 patients sampled, 35 fluid samples were analysed. Thirteen came from patients with pleural tuberculosis (6 confirmed, 7 probable) and 22 from patients without tuberculosis: 17 with cancer and 5 with community-acquired pneumonia. Two cancer patients had mesothelioma; the article gives no separate results for them and does not discuss asbestos. Two genes, RORA and RORC, had statistically significantly higher mRNA levels in tuberculosis fluid, by 3.38-fold and 3.42-fold. Most other genes were similar between the tuberculosis and non-tuberculosis groups. Cancer patients' fluid showed higher levels of several genes, including IL-4 and IL-6, and lower TGF-beta1. The authors concluded that RORA and RORC may be possible markers for telling tuberculous pleuritis apart from other common causes of exudative effusion, especially cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective study of gene expression (RT-qPCR) in pleural fluid samples
• Who was studied: Patients with exudative pleural effusions at a tertiary teaching hospital in southeast Brazil, over 12 months. The inclusion criterion was age over 18, but Table 1 lists a 12-year-old among the analysed patients. Pleural fluid was collected from 77 patients. Cytokine analysis was done on 35 samples: 13 from tuberculosis patients (6 confirmed, 7 probable) and 22 from non-tuberculosis patients (17 with cancer, 5 with community-acquired pneumonia). The cancer group included 2 patients with mesothelioma.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study compared cytokine and transcription-factor gene expression across diagnoses: tuberculosis, cancer and pneumonia.
• Main results:
  • RORA and RORC gene expression was statistically significantly higher in pleural fluid of tuberculosis patients than in non-tuberculosis patients (RORC p = 0.0241; RORA p = 0.0174).
  • In tuberculosis patients compared with non-tuberculosis patients, RORA showed a 3.38-fold increase and RORC a 3.42-fold increase.
  • For RORA, fold-change increases above 1.0, 2.0 and 3.0 in tuberculosis patients compared with controls gave odds ratios of 11.8, 33.3 and 24.5. No confidence intervals were reported.
  • For RORC, the same fold-change thresholds gave odds ratios of 4.8, 10.125 and 24.5. No confidence intervals were reported.
  • FOXP3 was the most induced gene in the regulatory T cell group in tuberculosis patients, but the difference was not statistically significant (p = 0.0704).
  • Apart from RORA and RORC, most gene expression in pleural fluid of tuberculosis patients was similar to that of non-tuberculosis patients.
  • Patients with pleural effusion related to cancer or metastatic disease had higher expression of IFN-alpha1, IFN-beta1, a TNF gene, IL-4 and IL-6, and lower expression of TGF-beta1. No p-values were given.
  • In pneumonia-associated effusions, IL-10 was induced, and IL-23, IFN-gamma, IL-12, FOXP3, IL-5, STAT3 and RORC were suppressed.
• The authors' conclusion: The authors concluded that RORA and RORC gene expression is involved in the immune response in pleural tuberculosis. They said these genes may be used as possible markers to distinguish tuberculous pleuritis from other common causes of exudative pleural effusion, especially malignant ones.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Cytokine, Pleural Effusion, Differential Diagnosis.

Related studies

• Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions — R. Thomas, H.M. Cheah, et al. (2016)
• Predicting Malignant and Paramalignant Pleural Effusions by Combining Clinical, Radiological and Pleural Fluid Analytical Parameters — S. Herrera Lara, E. Fernández-Fabrellas, et al. (2017)
• Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes — A.A. Shvedova, N. Yanamala, et al. (2016)
• Induction of altered mRNA expression profiles caused by fibrous and granular dust — S. Helmig, E. Dopp, et al. (2014)
• Tissue Xpert™ MTB/Rif assay is of limited use in diagnosing peritoneal tuberculosis in patients with exudative ascites — C. Bera, J.S. Michael, et al. (2015)
• MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion — G. Ak, S.C. Tomaszek, et al. (2015)

Browse more research in Lung, or return to medical research.