title: Multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection.
abstract: Cytokines play an important role in cell-mediated immune responses against Mycobacterium tuberculosis (Mtb) infection. Cytokine profile specifically associated with active tuberculosis (ATB) patients, subjects with latent tuberculosis infection (LTBI) and non-infected individuals remains to be determined.
  
  
  
  We enrolled a total of 92 subjects including patients with ATB (n = 25), LTBI (n = 36) and healthy controls (HC, n = 31) to investigate the cytokine production by peripheral blood mononuclear cells after Mtb purified protein derivative (PPD) stimulation which was evaluated by a beads-based multiplex assay system.
  
  
  
  The production of IL-1β, IL-2, IL-6, IL-10, IL-17, G-CSF, IFN-γ, IP-10, MIP-1α and TNF-α was abundantly induced by PPD in all three groups. The levels of IL-2, IL-10, IFN-γ, IP-10 and TNF-α were significantly higher in LTBI group than in ATB group. The combination of PPD-stimulated IL-2 and IL-10 accurately identified 84.0% of ATB and 88.9% of LTBI. We validated the use of PPD-stimulated IL-2 and IL-10 test combined with T-SPOT.TB test in a cohort of 44 subjects with TB suspicion. The sensitivity and specificity of the combined test were 83.3% and 92.3%, respectively. The PPD-stimulated IL-2/IFN-γ ratio (p < 0.001) in LTBI subjects was significantly higher than in active TB patients.
  
  
  
  Our study identified cytokine patterns characteristic of ATB and LTBI. Cytokines such as IL-2 and IL-10 may serve as biomarkers for distinguishing ATB from LTBI and healthy control and may contribute to intervention and improvement in TB diagnosis.
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Chanyi
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Shao
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: People's Hospital of Zhuji, Zhejiang Province, Zhuji 311800, China.
authors.forename: Zumo
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: People's Hospital of Zhuji, Zhejiang Province, Zhuji 311800, China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; MOH and MOE Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: pharmlife2002@yahoo.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; MOH and MOE Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: zhangwenhong@fudan.edu.cn.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014373:Tuberculin
keywords: Cytokines; Immunodiagnosis; Latent infection; Mycobacterium tuberculosis; Purified protein derivative