1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Persistent inflammation during anti-tuberculosis treatment with diabetes comorbidity

  1. Nathella Pavan Kumar
  2. Kiyoshi F Fukutani
  3. Basavaradhya S Shruthi
  4. Thabata Alves
  5. Paulo S Silveira-Mattos
  6. Michael S Rocha
  7. Kim West
  8. Mohan Natarajan
  9. Vijay Viswanathan
  10. Subash Babu
  11. Bruno B Andrade
  12. Hardy Kornfeld  Is a corresponding author
  1. National Institutes of Health, India
  2. Fundação José Silveira, Brazil
  3. Prof M Viswanathan Diabetes Research Center, India
  4. University of Massachusetts Medical School, United States
  5. National Institute for Research in Tuberculosis, India
Research Article
  • Cited 11
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Cite this article as: eLife 2019;8:e46477 doi: 10.7554/eLife.46477

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

  1. Nathella Pavan Kumar

    International Center for Excellence in Research, National Institutes of Health, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Kiyoshi F Fukutani

    Multinational Organization Network Sponsoring Translational and Epidemiological Research, Fundação José Silveira, Salvador, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Basavaradhya S Shruthi

    Prof M Viswanathan Diabetes Research Center, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Thabata Alves

    Multinational Organization Network Sponsoring Translational and Epidemiological Research, Fundação José Silveira, Salvador, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  5. Paulo S Silveira-Mattos

    Multinational Organization Network Sponsoring Translational and Epidemiological Research, Fundação José Silveira, Salvador, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael S Rocha

    Multinational Organization Network Sponsoring Translational and Epidemiological Research, Fundação José Silveira, Salvador, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Kim West

    University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5744-0280
  8. Mohan Natarajan

    National Institute for Research in Tuberculosis, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  9. Vijay Viswanathan

    Prof M Viswanathan Diabetes Research Center, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  10. Subash Babu

    International Center for Excellence in Research, National Institutes of Health, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  11. Bruno B Andrade

    Multinational Organization Network Sponsoring Translational and Epidemiological Research, Fundação José Silveira, Salvador, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6833-3811
  12. Hardy Kornfeld

    University of Massachusetts Medical School, Worcester, United States
    For correspondence
    Hardy.Kornfeld@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8970-7306

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.

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.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Received: February 28, 2019
  2. Accepted: June 20, 2019
  3. Accepted Manuscript published: July 4, 2019 (version 1)
  4. 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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