Clinical Correlates of Interferon Production in Patients with Tuberculosis

To determine if the capacity to produce interferon (IFN) gamma is related to the clinical manifestations of tuberculosis, we correlated Mycobacterium tuberculosis-induced IFN-gamma production by peripheral blood mononuclear cells (PBMCs) with clinical, radiographic, and laboratory variables for 63 human immunodeficiency virus (HIV)-negative patients and 43 HIV-positive patients with tuberculosis. For HIV-negative patients whose chest radiographs showed moderately advanced disease, the mean IFN-gamma concentration +/- SD was 1,639 +/- 388 pg/mL, whereas that for patients with far-advanced disease was 327 +/- 100 pg/mL (P = .0001). For HIV-infected patients who had only pleuropulmonary disease, the mean IFN-gamma concentration was 1,002 +/- 257 pg/mL, whereas that for patients with disease outside the lungs and pleura was 149 +/- 55 pg/mL (P = .0004). Multivariate analysis confirmed that the radiographic extent of disease and the site of disease were the only independent predictors of IFN-gamma production in HIV-negative and HIV-infected patients (P < or = .001). We conclude that reduced IFN-gamma production by PBMCs is a marker of severe tuberculosis in both HIV-negative and HIV-infected patients with tuberculosis.