Diagnostic Accuracy of Cytokine Levels (TNF-α, IL-2 and IFN-γ) in Bronchoalveolar Lavage Fluid of Smear-Negative Pulmonary Tuberculosis Patients

Abstract

Background: The determination of cytokine concentrations in serum and bronchoalveolar lavage fluid (BALF) may contribute to the diagnosis of tuberculosis (TB) since cytokines have been ascribed an important role in TB pathogenesis. Objective: To assess the diagnostic accuracy of TNF-α, IFN-γ and IL-2 levels in serum and BALF of smear-negative pulmonary TB patients. Method: BALF was obtained from the affected lobe in patients with smear-negative TB or other pulmonary diseases (OPD), and from the right middle lobe in healthy controls. ELISA and a nephelometric method were used to detect cytokine and albumin levels. Results: TNF-α levels in BALF were significantly elevated in the TB group (n = 15) compared with the OPD patients (n = 40) and controls (n = 17; p < 0.001). Although these three cytokines correlated well with each other in BALF (p < 0.0001, and r ≧ 0.7, respectively), BALF IL-2 and IFN-γ levels were not significantly different among the groups (p > 0.05). BALF TNF-α or IFN-γ levels were significantly higher in patients with cavitary disease (n = 11) versus those without (n = 61; p < 0.05). However, no significant difference was found between cavitary (n = 7) and non-cavitary TB in cytokine levels (p > 0.05). Neither gender nor smoking status showed any statistical differences in cytokines in the groups (p > 0.05). Sensitivity and specificity of BALF TNF-α were found to be 73 and 76%, respectively. The positive and negative predictive values for BALF TNF-α were 44 and 91%, respectively. Conclusion: In cases of smear-negative TB, BALF TNF-α can be a useful tool to identify healthy subjects rather than smear-negative TB patients.

Association of Antigen-Stimulated Release of Tumor Necrosis Factor-Alpha in Whole Blood with Response to Chemotherapy in Patients with Pulmonary Multidrug-Resistant Tuberculosis

“…These results are in agreement with other published results for IL-10 [10,11] and for TNF-α [12,13,14]. In contrast, IFN-γ and IL-12 levels were not different between healthy controls and TB patients.…”

Immunological Parameters to Define Infection Progression and Therapy Response in a Well-Defined Tuberculosis Model in Mice

“…1). At that time, numbers ofMtb in the lung of all mice had increased again up to 1.4x10 3 (range 1.0-6.8x10 3 ) , whereas in lout of 4 mice bacterial numbers in the spleen and liver had increased to numbers not significantly different from the untreated controls.…”

“…The role of cytokines in the host defence during TB was demonstrated in various studies in TB patients, showing levels of IFN-y, TNF-a, IL-4, IL-6 and IL-IO in serum, and BAL fluid as well as in pleural fluid. It is not clear whether these changes in cytokine expression are related to the infection progression and therapy response, and (if so) could possibly be useful markers (3)(4)(5)(6)(7). Monitoring cytokine levels in BAL fluid is hindered by the fact that the collection of BAL fluid from patients is an invasive procedure and is susceptible to inter-procedure variations.…”

Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels

“…However, IFN- γ assays using both pleural effusions [22] and peritoneal ascites [23] are considerably expensive, which may render this method less clinically useful and practical. Küpeli et al (2008) investigated a less expensive method of testing for cytokines as diagnostic biomarkers of Tb, using serum and bronchoalveolar lavage fluid (BALF) [24]. This study found a TNF- α cutoff of 17.6 pg/mL in serum and BALF (sensitivity: 73%; specificity: 76%) for distinguishing patients with smear-negative Tb from healthy subjects.…”