Cytokine polarization in miliary and pleural tuberculosis

Cytokines were measured in patients with pleural effusion and miliary tuberculosis (TB). Patients with pleural effusion had significantly higher interferon-gamma (IFN-gamma) levels (P < 0.001) in their pleural fluid as compared to that of peripheral blood of the same patients, thus exhibiting localization of predominantly Th1-type immunity in the pleural fluid. On the contrary, patients with miliary TB had higher IFN-γ levels in the peripheral blood as compared to their bronchoalveolar lavage fluid. Moreover, the median IFN-γ: IL-4 ratio in the peripheral blood of miliary TB patients was two-fold higher as compared to bronchoalveolar lavage fluid, suggesting that the cytokine profile at the disease site is skewed toward a Th2-like bias. Further, flow cytometry data revealed a significantly higher (P < 0.001) percentage of CD4(+) pleural fluid lymphocytes expressing IFN-gamma, whereas in the miliary TB, a nine-fold higher percentage of lymphocytes in bronchoalveolar lavage fluid expressed IL-4 in comparison with their peripheral CD4 T cells. Our data indicate, respectively, a Th1-like and Th2-like response in tuberculous pleural effusion and miliary TB, suggesting that these clinical forms of extrapulmonary tuberculosis probably reflect the extreme ends of a Th1-Th2 spectrum of the disease.