The impact of anti-tuberculous antibiotics and corticosteroids on cytokine production in QuantiFERON-TB Gold In Tube assays

被引:32
作者
Clifford, Vanessa [1 ,2 ]
Zufferey, Christel [1 ,2 ]
Germano, Susie [1 ,2 ]
Ryan, Norbert [3 ]
Leslie, David [3 ]
Street, Alan [4 ]
Denholm, Justin [4 ]
Tebruegge, Marc [1 ,2 ,5 ,6 ,7 ]
Curtis, Nigel [1 ,2 ]
机构
[1] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia
[2] Royal Childrens Hosp Melbourne, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia
[3] Victorian Infect Dis Reference Lab, Parkville, Vic, Australia
[4] Royal Melbourne Hosp, Victorian Infect Dis Unit, Parkville, Vic 3050, Australia
[5] Univ Southampton, Fac Med, Acad Unit Clin & Expt Med, Southampton SO9 5NH, Hants, England
[6] Univ Southampton, Natl Inst Hlth Res, Southampton Resp Biomed Res Unit, Southampton SO9 5NH, Hants, England
[7] Univ Southampton, Inst Life Sci, Southampton SO9 5NH, Hants, England
关键词
Mycobacterium tuberculosis; Tuberculosis; Immunomodulation; Diagnosis; Antibiotics; Cytokines; QuantiFERON-TB Gold; ACTIVE TUBERCULOSIS; RELEASE ASSAYS; CELL RESPONSE; CHILDREN; INFECTION; LATENT; PROTEIN-10; RIFAMPICIN; DIAGNOSIS; PEPTIDES;
D O I
10.1016/j.tube.2015.02.039
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction: 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-gamma and other potential cytokine biomarkers (TNF-alpha, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1 beta) 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-gamma) 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. Conclusion: Substantial changes in TB-antigen-induced IFN-gamma 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. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:343 / 349
页数:7
相关论文
共 33 条
[1]   Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: A case-control study [J].
Alsleben, Neele ;
Ruhwald, Morten ;
Ruessmann, Holger ;
Marx, Florian M. ;
Wahn, Ulrich ;
Magdorf, Klaus .
SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 2012, 44 (04) :256-262
[2]   Pretreatment of mice with rifampicin prolongs survival of endotoxic shock by modulating the levels of inflammatory cytokines [J].
An, Na ;
Song, Yu ;
Zhang, Xuemei ;
Ci, Xinxin ;
Li, Hongyu ;
Cao, Yongguo ;
Zhang, Mohan ;
Cui, Junqing ;
Deng, Xuming .
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, 2008, 30 (03) :437-446
[3]   Cytokine responses to quantiferon peptides in pediatric tuberculosis: A pilot study [J].
Armand, Marine ;
Chhor, Vibol ;
de Lauzanne, Agathe ;
Guerin-El Khourouj, Valerie ;
Pedron, Beatrice ;
Jeljeli, Mohamed ;
Gressens, Pierre ;
Faye, Albert ;
Sterkers, Ghislaine .
JOURNAL OF INFECTION, 2014, 68 (01) :62-70
[4]   Prednisolone Treatment Affects the Performance of the QuantiFERON Gold In-Tube Test and the Tuberculin Skin Test in Patients with Autoimmune Disorders Screened for Latent Tuberculosis Infection [J].
Belard, Erika ;
Semb, Synne ;
Ruhwald, Morten ;
Werlinrud, Anne Marie ;
Soborg, Bolette ;
Jensen, Frank Krieger ;
Thomsen, Henrik ;
Brylov, Annette ;
Hetland, Merete Lund ;
Nordgaard-Lassen, Inge ;
Ravn, Pernille .
INFLAMMATORY BOWEL DISEASES, 2011, 17 (11) :2340-2349
[5]   INTERFERON GAMMA-INDUCED PROTEIN-10 CONCENTRATIONS IN CHILDREN WITH PREVIOUS TUBERCULOSIS INFECTIONS AND DISEASE [J].
Bihari, Smiti ;
Cavalcanti, Nara ;
Correia, Jailson B. ;
Alves, Gerlane ;
Souza, Edvaldo ;
Brabin, Bernard J. ;
Cuevas, Luis E. .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2012, 31 (10) :1089-1091
[6]   Antirheumatic drugs and the risk of tuberculosis [J].
Brassard, Paul ;
Kezouh, Abbas ;
Suissa, Samy .
CLINICAL INFECTIOUS DISEASES, 2006, 43 (06) :717-722
[7]  
Cellestis, 2006, QUANTIFERON TB GOLD
[8]  
Chen DY, 2011, INT J TUBERC LUNG D, V15, P192
[9]   INTERFERON-γ RELEASE ASSAYS FOR THE DIAGNOSIS OF MYCOBACTERIUM TUBERCULOSIS INFECTION IN CHILDREN: A LITERATURE REVIEW [J].
Chiappini, E. ;
Bonsignori, F. ;
Accetta, G. ;
Boddi, V. ;
Galli, L. ;
Biggeri, A. ;
de Martino, M. .
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2012, 25 (02) :335-343
[10]  
Clifford V, 2015, TUBERCULOSIS