title: Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance.
abstract: Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-gamma) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-gamma levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-gamma levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-gamma immunoreactivities in serum followed kinetics in sputum. TNF-alpha, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-gamma, however, TNF-alpha and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.
authors.affiliation: Universidade Federal do Espírito Santo, Núcleo Doenças Infecciosas, Vitória, ES, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ribeiro-Rodrigues
authors.forename: Tatiana
authors.initials: T
authors.lastname: Resende Co
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ribeiro
authors.forename: Moises
authors.initials: M
authors.lastname: Palaci
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Sá
authors.forename: Ethel L
authors.initials: EL
authors.lastname: Maciel
authors.forename: Fausto E
authors.initials: FE
authors.lastname: Pereira Lima
authors.forename: Valderio
authors.initials: V
authors.lastname: Dettoni
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Dietze
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.forename: Christina S
authors.initials: CS
authors.lastname: Hirsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002452:Cell Count; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D013183:Sputum / Q000166:cytology / Q000276:immunology*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma