Diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion

Respirology. 2015 Jan;20(1):147-54. doi: 10.1111/resp.12414. Epub 2014 Oct 29.

Abstract

Background and objective: Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. While some inflammatory markers in pleural effusion (PE) are helpful in diagnosis, the roles of anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes have not been investigated.

Methods: Lymphocyte-predominant exudative PE samples were assayed for inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes. Logistic regression analysis was used to predict the probability of TPE and identify independently associated factors. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value for the predicted probability.

Results: Of 95 patients enrolled, 35 had TPE, 46 had malignant PE and 14 had PE due to other aetiologies. Interferon-γ (IFN-γ), adenosine deaminase (ADA), decoy receptor (DcR) 3, monocyte chemo-attractant protein (MCP)-1, IFN-induced protein (IP)-10, granzyme A and perforin were higher in TPE than in PE of other aetiologies. By logistic regression analysis, IFN-γ ≥ 75 pg/mL, ADA ≥ 40 IU/mL, DcR3 ≥ 9.3 ng/mL and soluble tumour necrosis factor receptor 1 (TNF-sR1) ≥ 3.2 ng/mL were independent factors associated with TPE. The predicted probability based on the four predictors had an area under the ROC curve of 0.920, with 82.9% sensitivity and 86.7% specificity under the cut-off value of 0.303. In the TPE group, patients with positive PE/pleural culture for Mycobacterium tuberculosis had higher pleural IFN-γ, MCP-1, IP-10 and perforin than those with positive sputum but negative PE culture.

Conclusions: While pleural interferon-γ and ADA are conventional markers for diagnosing TPE, simultaneous measurements of DcR3 and TNF-sR1 can improve the diagnostic efficacy.

Keywords: adenosine deaminase; decoy receptor 3; interferon-γ; soluble tumour necrosis factor receptor 1; tuberculous pleural effusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / metabolism
  • Aged
  • Biomarkers / metabolism
  • Female
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis* / isolation & purification
  • Mycobacterium tuberculosis* / pathogenicity
  • Perforin / metabolism
  • Pleural Effusion* / diagnosis
  • Pleural Effusion* / etiology
  • Pleural Effusion* / metabolism
  • Pleural Effusion* / physiopathology
  • ROC Curve
  • Receptors, Tumor Necrosis Factor, Member 6b / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I / blood*
  • Sensitivity and Specificity
  • T-Lymphocytes, Cytotoxic / pathology*
  • Tuberculosis, Pleural* / complications
  • Tuberculosis, Pleural* / diagnosis
  • Tuberculosis, Pleural* / metabolism
  • Tuberculosis, Pleural* / physiopathology

Substances

  • Biomarkers
  • Receptors, Tumor Necrosis Factor, Member 6b
  • Receptors, Tumor Necrosis Factor, Type I
  • Perforin
  • Interferon-gamma
  • Adenosine Deaminase