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

Extrapulmonary tuberculosis is presumably a marker of underlying immunodefi ciency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from hum an 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)- gamma production, interleukin (IL)-12 production, and -gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case pat ients and control patients. However, median resting IL-8 production was sig nificantly lower in case patients than control patients (8051 vs. 19,290 pg /mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha res ponse was lower in case patients than control patients after stimulation wi th lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide pl us IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting I L-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several year s after cure of disease, suggesting an abnormality in innate immunity.