Vanessa Clifford1, Christel Zufferey1, Susie Germano1, Norbert Ryan2, David Leslie2, Alan Street3, Justin Denholm3, Marc Tebruegge4, Nigel Curtis5. 1. Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia. 2. Victorian Infectious Diseases Reference Laboratory, Parkville, VIC, Australia. 3. Victorian Infectious Diseases Unit, The Royal Melbourne Hospital, Parkville, VIC, Australia. 4. 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. 5. 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.
Abstract
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-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. CONCLUSION: 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. Crown
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-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. CONCLUSION: 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. Crown
Authors: Edward Barton; Yifang Gao; Darran Ball; Katy Fidler; Nigel Klein; Nigel Curtis; Vanessa Clifford; Ben G Marshall; Andrew Chancellor; Salah Mansour; Paul Elkington; Marc Tebruegge Journal: Ann Am Thorac Soc Date: 2019-06
Authors: Julia Steiger; Alexander Stephan; Megan S Inkeles; Susan Realegeno; Heiko Bruns; Philipp Kröll; Juliana de Castro Kroner; Andrea Sommer; Marina Batinica; Lena Pitzler; Rainer Kalscheuer; Pia Hartmann; Georg Plum; Steffen Stenger; Matteo Pellegrini; Bent Brachvogel; Robert L Modlin; Mario Fabri Journal: J Immunol Date: 2016-05-27 Impact factor: 5.422
Authors: Noëmi R Meier; Thomas Volken; Marc Geiger; Ulrich Heininger; Marc Tebruegge; Nicole Ritz Journal: Front Pediatr Date: 2019-05-29 Impact factor: 3.418
Authors: Jun Won Park; Jeffrey R Curtis; Hajeong Lee; Jung-Kyu Lee; Yeong Wook Song; Eun Bong Lee Journal: PLoS One Date: 2020-12-31 Impact factor: 3.240
Authors: Steven B Welch; Marc Tebruegge; Alasdair Bamford; Garth Dixon; Nigel Klein; Stephen D Marks; Nicole Ritz Journal: Pediatr Nephrol Date: 2020-11-27 Impact factor: 3.714