Regular Article| Volume 95, ISSUE 7, P577-581, July 2001

Download started.


Cytokines in pleural liquid for diagnosis of tuberculous pleurisy

      This paper is only available as a PDF. To read, Please Download here.


      An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor α (TNF α) and interferon γ (IFNγ ) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNF α and IFN γ levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0·770, 0·875, 0·892 and 0·987, respectively for IL-8, TNF α, ADA and IFN γ,. No false-positives were encountered with IFN γ and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFN γ is a very reliable marker of tuberculous pleurisy.




        • Sahn SA
        Pleural diagnostic techniques.
        Curr Opin Pulmon Med. 1995; 1: 324-330
        • Light RW
        Diagnostic principles in pleural disease.
        Eur Resp J. 1997; 10: 476-481
        • Kuralay F
        • Comlekci A
        Adenosine deaminase activity: adenosine deaminase activity: a useful marker in distinguishing pleural effusions due to malignancy from tuberculosis.
        Biochem Soc Trans. 1998; 26: S163
        • Valdes L
        • Alvarez D
        • San Jose E
        Value of adenosine deaminase in the diagnosis of tuberculous pleural effusions in young patients in a region of high prevalence of tuberculosis [see comments].
        Thorax. 1995; 50: 600-603
        • Burgess LJ
        • Maritz FJ
        • Le Roux I
        • Taljaard JJ
        Use of adenosine deaminase as a diagnostic tool for tuberculous pleurisy [see comments].
        Thorax. 1995; 50: 672-674
        • Banales JL
        • Pineda PR
        • Fitzgerald JM
        Adenosine deaminase in the diagnosis of tuberculous pleural effusions.
        Chest. 1991; 99: 355-357
        • Hayashi M
        • Nagai A
        • Kobayashi K
        • Sawai T
        • Konno K
        Utility of polymerase chain reaction for diagnosis of tuberculous pleural effusion.
        Nippon Kyobu Shikkan Gakkai Zasshi—Jap J Thor Dis. 1995; 33: 253-256
        • Naito T
        • Ohtuka M
        • Ishikawa H
        • Satoh H
        • Hasegawa S
        Clinical significance of cytokine measurement in pleural effusion.
        Kekkakku. 1997; 72: 565-572
        • Shimokata K
        • Saka H
        • Murate T
        • Hasegawa Y
        • Hasegawa T
        Cytokine content in pleural effusion.
        Chest. 1991; 99: 1103-1107
        • Dlugovitzky D
        • Rateni L
        • Torres-Morales A
        Levels of interleukin-8 in tuberculous pleurisy and the profile of immunocompetent cells in pleural and peripheral compartments.
        Immunol Letts. 1997; 55: 35-39
        • Friedland J
        • Remick
        • Shattock R
        • Griffin G
        Secretion of interleukin-8 following phagocytosis of Mycobacterium tuberculosis by human monocyte cell lines.
        Eur J Immunol. 1992; 22: 1373-1378
        • Segura RM
        • Alegre J
        • Varela
        Interleukin-8 and markers of neutrophil degranulation in pleural effusions.
        Am J Resp Crit Care Med. 1998; 157: 1565-1572
        • Ashitani J
        • Mukae H
        • Nakazato M
        Elevated pleural fluid levels of defensins in patients with empyema.
        Chest. 1998; 113: 788-794
        • Ceyhan BB
        • Ozgun S
        • Celikel T
        • Yalcin M
        • Koc M
        IL-8 in pleural effusion.
        Respir Med. 1996; 90: 215-221
        • Ogawa K
        • Koga H
        • Yang B
        Differential diagnosis of tuberculous pleurisy by the measurement of cytokine concentration in pleural effusion.
        Kekkaku. 1996; 71: 663-669
        • Orphanidou D
        • Gaga M
        • Rasidakis A
        Tumour necrosis factor, interleukin-1 and adenosine deaminase in tuberculous pleural effusion.
        Respir Med. 1996; 90: 95-98
        • Soderblom T
        • Nyberg P
        • Teppo AM
        • Klockars M
        • Riska H
        • Pettersson T
        Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous and rheumatoid pleurisy.
        Eur Resp J. 1996; 9: 1652-1665
        • Naito T
        • Ohtsuka M
        • Ishikawa H
        • Satoh H
        • Hasegawa S
        Clinical significance of cytokine measurement in pleural effusion.
        Kekkaku. 1997; 72: 565-572
        • Meeda J
        • Ueki N
        • Ohkawa T
        Local production and localization of transforming growing factor-beta in tuberculous pleurisy.
        Clin Exp Immunol. 1993; 92: 32-38
        • Esteban R
        • Teresa E
        • Jose MM
        • Immaculada O
        • Gloria E
        Lymphocyte proliferation and gamma-interferon production after ‘in-vitro’ stimulation with PPD.
        Chest. 1990; 137: 1381-1385
        • Peter FB
        • Sameer DM
        • Cathleen LC
        • Claude P
        • Thomas HR
        • Robert LM
        Compartmentalization of a CD4 T lymphocyte subpopulation in tuberculous pleuritis.
        J Immunol. 1989; 142: 1114-1119
        • Kim YC
        • Park KO
        • Bom HS
        Combining ADA, protein and IFN-gamma best allows discrimination between tuberculous and malignant pleural effusion.
        Korean J Int Med. 1997; 12: 225-231
        • Luis V
        • Esther SJ
        • David A
        Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma.
        Chest. 1933; 103: 458-465
        • Wu-Huei H
        • Chi-Der C
        • Woan-Tzy C
        • Chyong-Fen C
        Diagnostic value of adenosine deaminase and gamma-interferon in tuberculous and malignant pleural effusions.
        J Formosan Med Assoc. 1989; 89: 879-882
        • Esteban R
        • Inmaculada O
        • Jose M
        High level of interferon gamma in tuberculous pleural effusion.
        Chest. 1988; 193: 308-311
        • Shimokata K
        • Kishimoto H
        • Takagi E
        • Tsunekawa H
        Determination of the T-cell subset producing γ -interferon in tuberculous effusion.
        Microbiol Immunol. 1986; 30: 353-361
        • Ogawa K
        • Koga H
        • Hirakata Y
        • Tomono K
        • Tashiro T
        • Kohno S
        Differential diagnosis of tuberculous pleurisy by measurement of cytokine concentrations in pleural effusions.
        Tubercle Lung Dis. 1997; 78: 29-34
        • Matsuo S
        • Takahashi H
        Practical application of receiver characteristic curve on laboratory diagnosis.
        Jpn J Clin Pathol. 1994; 42: 585-590