Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses

Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-γ production, interleukin (IL)-12 production, and IFN-γ receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19, 290 pg/mL; P = .009). In addition, the median tumor necrosis factor (TNF)-α response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P = .06) and lipopolysaccharide plus IFN-γ (3301 vs. 4411 pg/mL; P = .04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-α production were not associated with IFN-γ or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.