title: Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses.
abstract: 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)-gamma production, interleukin (IL)-12 production, and IFN-gamma 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)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA. tsterls@jhmi.edu
authors.forename: T R
authors.initials: TR
authors.lastname: Sterling
authors.forename: S E
authors.initials: SE
authors.lastname: Dorman
authors.forename: R E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.forename: J
authors.initials: J
authors.lastname: Hackman
authors.forename: K
authors.initials: K
authors.lastname: Moore
authors.forename: S M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D018023:HIV Seronegativity; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D016207:Cytokines