Persistent inflammation during anti-tuberculosis treatment with diabetes comorbidity
Nathella Pavan Kumar,
Kiyoshi F Fukutani,
Basavaradhya S Shruthi,
Thabata Alves,
Paulo S Silveira-Mattos,
Michael S Rocha,
Kim West,
Mohan Natarajan,
Vijay Viswanathan,
Subash Babu,
Bruno B Andrade,
Hardy Kornfeld
Affiliations
Nathella Pavan Kumar
National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research, Chennai, India
Kiyoshi F Fukutani
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), Fundação José Silveira, Salvador, Brazil; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil; Faculdade de Tecnologia e Ciências, Salvador, Brazil
Basavaradhya S Shruthi
Prof. M. Viswanathan Diabetes Research Center, Chennai, India
Thabata Alves
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), Fundação José Silveira, Salvador, Brazil; Universidade Salvador, Laureate Universities, Salvador, Brazil
Paulo S Silveira-Mattos
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), Fundação José Silveira, Salvador, Brazil; Faculdade de Tecnologia e Ciências, Salvador, Brazil
Michael S Rocha
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), Fundação José Silveira, Salvador, Brazil
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), Fundação José Silveira, Salvador, Brazil; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil; Faculdade de Tecnologia e Ciências, Salvador, Brazil; Universidade Salvador, Laureate Universities, Salvador, Brazil
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.
