title: Type 2 diabetes mellitus coincident with pulmonary tuberculosis is associated with heightened systemic type 1, type 17, and other proinflammatory cytokines.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 International Center for Excellence in Research, National Institutes of Health.
authors.forename: Nathella Pavan
authors.initials: NP
authors.lastname: Kumar
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.forename: Mohideen S
authors.initials: MS
authors.lastname: Jawahar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D006442:Glycated Hemoglobin; D018836:Inflammation Mediators; D007371:Interferon-gamma; D016753:Interleukin-10; D020381:Interleukin-17; D020382:Interleukin-18; D053583:Interleukin-1beta; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C508609:IL10 protein, human; C508717:IL17A protein, human; C508585:IL1B protein, human; C508594:IL2 protein, human; C508599:IL5 protein, human; C508600:IL6 protein, human; C517652:hemoglobin A1c protein, human