title: The impact of anti-tuberculous antibiotics and corticosteroids on cytokine production in QuantiFERON-TB Gold In Tube assays.
abstract: BACKGROUND
  The ability to monitor and confirm adequate treatment of latent TB infection (LTBI) would be a major advance. The potential immunomodulatory effects of anti-tuberculous drugs and steroids need to be considered in assessing the utility of cytokine-based assays for this purpose.
  
  
  METHODS
  We determined whether anti-tuberculous antibiotics or dexamethasone affect the production of IFN-γ and other potential cytokine biomarkers (TNF-α, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β) in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay. Blood from ten adults with LTBI was added to one standard set of QFT-IT tubes and five further sets containing therapeutic concentrations of either isoniazid, rifampicin, isoniazid and rifampicin, ciprofloxacin or dexamethasone. Resulting supernatants were analysed by ELISA (QFT-IT assay IFN-γ) and xMAP-Luminex assays (all cytokines).
  
  
  RESULTS
  Anti-tuberculous antibiotics had only a limited effect on categorical QFT-IT assay results and the production of cytokines. In contrast, dexamethasone resulted in a change in categorical results from positive to negative in four of ten patients, and caused a marked reduction in IL-13 and IL-1ra responses.
  
  
  CONCLUSIONS
  Substantial changes in TB-antigen-induced IFN-γ and other cytokine responses during treatment likely primarily reflect host immunological changes rather than immunomodulatory effects of anti-tuberculous antibiotics. Results from cytokine-based assays in patients on corticosteroids should be interpreted with caution.
authors.affiliation: Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Clifford
authors.affiliation: Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
authors.forename: Christel
authors.initials: C
authors.lastname: Zufferey
authors.affiliation: Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
authors.forename: Susie
authors.initials: S
authors.lastname: Germano
authors.affiliation: Victorian Infectious Diseases Reference Laboratory, Parkville, VIC, Australia.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ryan
authors.affiliation: Victorian Infectious Diseases Reference Laboratory, Parkville, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Leslie
authors.affiliation: Victorian Infectious Diseases Unit, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Street
authors.affiliation: Victorian Infectious Diseases Unit, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Justin
authors.initials: J
authors.lastname: Denholm
authors.affiliation: Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia; Academic Unit of Clinical and Experimental Medicine, Faculty of Medicine & National Institute for Health Research Southampton Respiratory Biomedical Research Unit & Institute for Life Sciences, University of Southampton, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Tebruegge
authors.affiliation: Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia. Electronic address: nigel.curtis@rch.org.au.
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D003907:Dexamethasone / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008297:Male; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000904:Antibiotics, Antitubercular; D015415:Biomarkers; D016207:Cytokines; C573415:IFNG protein, human; D003907:Dexamethasone; D007371:Interferon-gamma
keywords: Antibiotics; Cytokines; Diagnosis; Immunomodulation; Mycobacterium tuberculosis; QuantiFERON-TB Gold; Tuberculosis