Type 2 diabetes mellitus coincident with pulmonary tuberculosis is associated with heightened systemic type 1, type 17, and other proinflammatory cytokines

Ann Am Thorac Soc. 2013 Oct;10(5):441-9. doi: 10.1513/AnnalsATS.201305-112OC.

Abstract

Rationale: Type 2 diabetes mellitus is a major risk factor for the development of active tuberculosis, although the biological basis underlying this susceptibility remains poorly characterized.

Objectives and methods: To identify the influence of coincident diabetes mellitus on cytokine levels in pulmonary tuberculosis, we examined circulating levels of a panel of cytokines and chemokines in the plasma of individuals with tuberculosis with diabetes and compared them with those of individuals without diabetes.

Measurements and main results: Tuberculosis with diabetes is characterized by elevated circulating levels of type 1 (IFN-γ, tumor necrosis factor-α, and IL-2), type 2 (IL-5), and type 17 (IL-17A) cytokines but decreased circulating levels of IL-22. This was associated with increased systemic levels of other proinflammatory cytokines (IL-1β, IL-6, and IL-18) and an antiinflammatory cytokine (IL-10) but not type 1 IFNs. Moreover, tuberculosis antigen-stimulated whole blood also showed increased levels of proinflammatory cytokines. Finally, type 1 and type 17 cytokines in plasma exhibit a significant positive correlation with hemoglobin A1C levels, indicating that impaired control of diabetes is associated with this proinflammatory milieu. Multivariate analysis revealed that the association of proinflammatory cytokines with diabetes mellitus was not influenced by age, sex, or other metabolic parameters.

Conclusions: Our data reveal that tuberculosis with diabetes is characterized by heightened cytokine responsiveness, indicating that chronic inflammation underlying type 2 diabetes potentially contributes to increased immune pathology and poor control in tuberculosis infection.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cohort Studies
  • Cytokines / immunology*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Inflammation / immunology
  • Inflammation Mediators / immunology*
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-17 / immunology
  • Interleukin-18 / immunology
  • Interleukin-1beta / immunology
  • Interleukin-2 / immunology
  • Interleukin-5 / immunology
  • Interleukin-6 / immunology
  • Interleukins / immunology
  • Male
  • Middle Aged
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Young Adult

Substances

  • Cytokines
  • Glycated Hemoglobin A
  • IL10 protein, human
  • IL17A protein, human
  • IL1B protein, human
  • IL2 protein, human
  • IL5 protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-18
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-5
  • Interleukin-6
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • hemoglobin A1c protein, human
  • Interleukin-10
  • Interferon-gamma
  • interleukin-22