Interleukin-6, Interleukin-17 and Transforming Growth Factor-Beta are Overexpressed in Newly Diagnosed Tuberculosis Patients; Potent Biomarkers of Mycobacterial Infection

Cytokines, as key regulators of immune responses, are imbalanced in tuberculosis (TB) which may reflect the status of the disease. Therefore, cytokines could be introduced as potential diagnostic and prognostic TB biomarkers.

Here, we examined the plasma levels of IL-17, IL-6, and TGF-β among newly diagnosed patients with TB in comparison to normal subjects and analyzed the diagnostic utility of each cytokine to introduce a novel TB biomarker.

A total of 105 smear-positive, including 78 newly diagnosed (ND) and 27 under treatment (UT) patients with pulmonary TB and 111 age- and sex-matched healthy subjects were recruited. ELISA cytokine assay was used to determine the plasma levels of IL-17, IL-6, and TGF-β.

IL-6 plasma level was higher in the ND patients than healthy subjects (P = 0.002) and the UT patients (P < 0.0001). Also, IL-17 and TGF-β were significantly overexpressed among both groups of patients with TB compared with healthy subjects. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic utility of the evaluated cytokines. Area under the curve (AUC) for IL-6 was 0.5598 (P = 0.129). Regarding the diagnostic value of IL-6 to distinguish between the ND and UT patients, AUC for IL-6 was 0.8139 (P < 0.0001). Setting the optimal cut-off value at 23.75 gave a sensitivity of 77.78% and a specificity of 74.36%. AUC for IL-17 was 0.9148 (P < 0.0001), while AUC for TGF-β was 0.8877 (P < 0.0001). Setting the optimal cut-off value at 14.05 for IL-17 gave a sensitivity of 81.90% and a specificity of 79.28%, while setting the optimal cut-off value at 51.20 for TGF-β resulted in a sensitivity of 82.69% and a specificity of 72.73%.

All evaluated cytokines were overexpressed in newly diagnosed TB patients with different diagnostic utilities. IL-6 is more convenient in distinguishing the ND from UT patients. IL-17 is more specific in distinguishing TB infection and TGF-β represented a higher sensitivity. It is suggested that multiple cytokine assay should be conducted to have a better diagnostic performance rather than individual cytokine evaluation.