Heterogeneity in the cytokine profile of tuberculosis – diabetes co-morbidity

• Published in: Cytokine (Philadelphia, Pa.) Vol. 125; p. 154824
• Main Authors: Kumar, Nathella P., Moideen, Kadar, Nancy, Arul, Viswanathan, Vijay, Shruthi, Basavaradhya S., Sivakumar, Shanmugam, Natarajan, Mohan, Kornfeld, Hardy, Babu, Subash
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2020
• Subjects: Adult; Aged; Bacterial; Blood Glucose - metabolism; Comorbidity; Cytokines; Cytokines - blood; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Down-Regulation; Female; Glycated Hemoglobin A - metabolism; Humans; Interferon-gamma - blood; Interleukin-17 - blood; Interleukin-1alpha - blood; Interleukin-1beta - blood; Interleukin-6 - blood; Male; Middle Aged; Tuberculosis; Tuberculosis - blood; Tuberculosis - complications; Tuberculosis - immunology; Tuberculosis - therapy; Tumor Necrosis Factor-alpha - blood; Up-Regulation; Bacterial; Tuberculosis; Cytokines; Diabetes mellitus
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2019.154824

•Tuberculosis – diabetes co-morbidity is characterized by heterogeneity in both biochemical and immunological responses with newly diagnosed diabetic individuals with TB (TB-NDM) exhibiting significant differences from known diabetic individuals at incident TB (TB-KDM).•TB-NDM individuals have significantly lower levels of blood glucose and HbA1c in comparison to TB-KDM individuals.•TB-NDM individuals have significantly lower levels of unstimulated and TB-antigen stimulated pro-inflammatory cytokines in comparison to TB-KDM individuals.•This biochemical and cytokine pattern persists even after anti-tuberculosis treatment and consequent cure. Tuberculosis – diabetes (TB-DM) co-morbidity is characterized by heterogeneity in clinical and biochemical parameters between newly diagnosed diabetic individuals with TB (TB-NDM) and known diabetic individuals at incident TB (TB-KDM). However, the immunological profile underlying this heterogeneity is not explored. To identify the cytokine profiles in TB-NDM and TB-KDM individuals, we examined the plasma cytokine levels as well as TB-antigen stimulated levels of pro-inflammatory cytokines. TB-KDM individuals exhibit significantly higher levels of IFNγ, IL-2, TNFα, IL-17A, IL-1α, IL-1β and IL-6 in comparison to TB-NDM, TB alone and DM alone individuals. TB-NDM individuals are characterized by significantly lower levels of blood glucose and glycated hemoglobin in comparison to TB-KDM with both groups exhibiting a significant lowering of glycated hemoglobin levels at 6  months of anti-tuberculosis therapy (ATT). TB-NDM individuals are characterized by significantly diminished – unstimulated levels of IFNγ, IL-2, TNFα, IL-17A, IL-1α, IL-1β and IL-12 at pre-treatment, of IFNγ, IL-2 and IL-1α at 2  months of ATT and IL-2 at post-treatment in comparison to TB-KDM. TB-NDM individuals are also characterized by significantly diminished TB-antigen stimulated levels of IFNγ, IL-2, TNFα, IL-17A, IL-17F, IL-1α, IL-1β and/or IL-6 at pre-treatment and at 2  months of ATT and IFNγ, IL-2, IL-1α and IL-1β at post-treatment. In addition, TB-NDM individuals are characterized by significantly diminished mitogen – stimulated levels of IL-17F and IL-6 at pre-treatment and IL-6 alone at 6 months of ATT. Therefore, our data reveal considerable heterogeneity in the immunological underpinnings of TB-DM co-morbidity. Our data also suggest that TB-NDM exhibits a characteristic profile, which is both biochemically and immunologically distinct from TB-KDM.