Increased TNF-α, IL-1β and IL-6 levels in the bronchoalveolar lavage fluid with the upregulation of their mRNA in macrophages lavaged from patients with active pulmonary tuberculosis

Setting: We hypothesized that patients with active pulmonary tuberculosis (TB) have tubercular pneumonitis and that alveolar macrophages at these sites release proinflammatory cytokines, resulting in high levels of cytokines in alveolar epithelial lining fluid. Objective: To measure cytokine levels in bronchoalveolar lavage fluid (BALF) and to confirm the source of any cytokines by examination of alveolar macrophage cytokine mRNA. Design: Seventeen active pulmonary TB patients and 15 healthy controls were prospectively studied. Bronchoalveolar lavage (BAL) was performed, proinflammatory cytokine levels were determined and alveolar macrophages isolated from BALF were prepared for RNA extraction and Northern blot analysis. Results: Compared with healthy controls, TNF-α, IL-1β and IL-6 in BALF were all significantly higher in patients with active pulmonary TB, 298.7 ± 85.9 vs. 8.9 ± 2.7 (P = 0.0001); 164.4 ± 67.5 vs. 8.9 ± 2.7 (P = 0.003); 969.2 ± 214.2 vs. 86.4 ± 17.0 (mean ± SE pg/ml) (P=0.0001), respectively. Only TNF-α and IL-6 levels were significantly higher in sera of active pulmonary TB patients, 92.3 ± 28.7 vs. 3.5 ± 1.2; 15.2 ± 5.4 vs. 2.1 ± 2.1, respectively. Northern blot analysis revealed increased gene expression of these alveolar macrophage cytokines in patients with active pulmonary TB compared healthy controls. Conclusion: Significantly higher levels of TNF-α, IL-1β and IL-6 were found in BALF from patients with active pulmonary TB, and were released by alveolar macrophages in the TB lesions.