Persistent inflammation during anti-tuberculosis treatment with diabetes comorbidity
- National Institutes of Health, India
- Fundação José Silveira, Brazil
- Prof M Viswanathan Diabetes Research Center, India
- University of Massachusetts Medical School, United States
- National Institute for Research in Tuberculosis, India
Abstract
Diabetes mellitus (DM) increases risk for pulmonary tuberculosis (TB) and adverse treatment outcomes. Systemic hyper-inflammation is characteristic in people with TB and concurrent DM (TBDM) at baseline, but the impact of TB treatment on this pattern has not been determined. We measured 17 plasma cytokines and growth factors in longitudinal cohorts of Indian and Brazilian pulmonary TB patients with or without DM. Principal component analysis revealed virtually complete separation of TBDM from TB individuals in both cohorts at baseline, with hyper-inflammation in TBDM that continued through treatment completion at six months. By one year after treatment completion, there was substantial convergence of mediator levels between groups within the India cohort. Non-resolving systemic inflammation in TBDM comorbidity could reflect delayed lesion sterilization or non-resolving sterile inflammation. Either mechanism portends unfavorable long-term outcomes including risk for recurrent TB and for damaging immune pathology.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 through 5.
Article and author information
Author details
Funding
CRDF Global (USB1-31149-XX-13)
- Hardy Kornfeld
CRDF Global (USB1-31149-XX-13)
- Vijay Viswanathan
National Institutes of Health (U01AI115940)
- Bruno B Andrade
Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Kiyoshi F Fukutani
Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Thabata Alves
Fundação de Amparo à Pesquisa do Estado da Bahia
- Paulo S Silveira-Mattos
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Kiyoshi F Fukutani
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Bruno B Andrade
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Ethics
Human subjects: All research presented here was conducted according to the principles expressed in the Declaration of Helsinki. The Indian cohort study was approved by the Ethics Committee of the Prof. M. Viswanathan Diabetes Research Centre (ECR/51/INST/TN/2013/MVDRC/01). The Brazilian cohort study was approved by the Ethics Committee of the Maternidade Climério de Oliveira, Federal University of Bahia (CAAE: 0115.0.054.000-09). Written informed consent was obtained from all participants at both sites.
Version history
- Received: February 28, 2019
- Accepted: June 20, 2019
- Accepted Manuscript published: July 4, 2019 (version 1)
- Version of Record published: July 26, 2019 (version 2)
Copyright
© 2019, Kumar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Persistent inflammation during anti-tuberculosis treatment with diabetes comorbidity
eLife 8:e46477.
https://doi.org/10.7554/eLife.46477
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