IFN-gamma and IL-12 are increased in active compared with inactive tuberculosis

Cytokine-mediated immune responses to Mycobacterium tuberculosis infection are important determinants of M. tuberculosis disease development and pathology. However, the distinction between changes in cytokine profile attributable to M. tuberculosis infection and those associated with active pulmonary tuberculosis is unclear. We have compared T cells and their subsets, macrophages, and cytokine messenger RNA (mRNA) profile in the bronchoalveolar lavage (BAL) of patients with active pulmonary tuberculosis with inactive tuberculosis subjects. Ten patients with microbiologically confirmed active pulmonary tuberculosis and 25 subjects with inactive tuberculosis were recruited. Bronchoscopy with BAL was undertaken in all cases and BAL cytospins were examined using the techniques of immunocytochemistry and in situ hybridization. There was a significant increase in the percentage of BAL cells that were CD8+ T cells in active tuberculosis compared with inactive tuberculosis (mean +/- SEM: 7.2 +/- 0.9 versus 2.1 +/- 0.4, p < 0.001), but not CD3+ or CD4+ T cells nor macrophages. There were significant increases in the percentage of BAL cells expressing mRNA for interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) in active versus inactive pulmonary tuberculosis subjects (8.0 +/- 0.6 versus 3.7 +/- 0.4 and 28.4 +/- 2.3 versus 10.2 +/- 1.0, p < 0.001, respectively). There were no significant differences between the active and inactive groups in the number of cells expressing mRNA for IL-2, tumor necrosis factor-alpha (TNF-alpha), IL-4, and IL-5. In conclusion, active pulmonary tuberculosis is associated with increased numbers of CD8+ cells and marked increases in the expression of IL-12 and IFN-gamma mRNA in the BAL, both of which may be useful markers of disease activity.