Background Previous studies reported interleukin-27 （IL-27）, interferon-y （IFN-γ）, or adenosine deaminase （ADA） alone plays a helpful role in diagnosing tuberculous pleural effusion （TPE）. The present study aims at comparing the diagnostic accuracy of pleural IL-27, IFN-γ, and ADA, and investigate the diagnostic accuracy of the combination of IL-27, IFN-γ, or/ and ADA for differentiating TPE from pleural effusions with the other etiologies. Methods The concentrations of IL-27, IFN-γ and ADA were simultaneously determined in pleural fluids and sera from 40 patients with TPE; 26 with malignant pleural effusion, seven with infectious pleural effusion, and eight with transudative pleural effusion by enzyme linked immunosorbent assay and colorimetric method. The corresponding biochemical indexs were also simultaneously determined. Results The concentrations of pleural IL-27 and IFN-γ in the tuberculous group were significantly higher than those in the malignant, infectious, and transudative groups. The concentrations of ADA in TPE were significantly higher than those in MPE or transudative effusions, while much lower than those in infectious effusions. Among these three biomarkers, IL- 27 was the most effective for TPE diagnosis, with the cut off value of 900.8 ng/L. IL-27 had a high sensitivity of 95% and specificity of 97.6% for differential diagnosis of TPE from non-TPEs. Combinations of IL-27, IFN-γ and ADA measurements further increased the sensitivity or specificity up to 100%. Conclusions Compared to non-TPEs, IL-27, IFN-γ and ADA all simultaneously increased in TPE; and among these three rapid detection methods, IL-27 appeared to be the best for distinguishing tuberculous from non-TPEs, especially from MPE. Combinations of the three markers （IL-27, IFN-γ and ADA） yielded the highest sensitivity and specificity. These findings suggest that the applications of a new biomarker, IL-27, alone or with IFN-γ and ADA, may contribute to more efficient diagnosis strategies in the management
