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Immune Response to TB Antigen Stimulation in Type 2 Diabetes Mellitus: Insights from a Cross-Sectional Cytokine

Nanny Natalia Mulyani Soetedjo¹, Raspati Cundarani Koesoemadinata², Nofri Rahmadika³

¹Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Dr Hasan Sadikin General Hospital, Bandung, Indonesia.

Journal of Inflammation Research

|December 29, 2025

Abstract

Purpose:

The syndemic of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) presents a growing global health challenge, particularly in high-burden countries. T2DM is known to impair immune responses, increasing susceptibility to TB. However, the cytokine dynamics underlying this interaction remain unclear. This study aimed to explore the differences in ex vivo cytokine responses between individuals with and without T2DM following TB antigen stimulation.

Patients And Methods:

In this cross-sectional study, we analyzed plasma samples from 110 individuals with T2DM and 38 without, collected as part of the TANDEM and INFECT cohort studies in Indonesia. Cytokine levels (IL-1β, IL-6, TNF-α, and IFN-γ) were measured using ELISA before and after TB antigen stimulation using the QuantiFERON-TB Gold assay. Demographic, clinical, and metabolic parameters were recorded. Statistical analyses included Mann-Whitney U-tests and Spearman correlation.

Results:

Patients with DM showed a higher baseline levels of pro-inflammatory cytokines than non-DM individuals, particularly in IL-1β, IL-6 and TNF-α, suggesting a primed immune response even before TB antigen exposure. After TB antigen stimulation, no significant between-group differences were observed in cytokine levels. However, IL-1β showed a more pronounced median increase in T2DM (124 vs -54 pg/mL, p = 0.43), while IL-6, TNF-α, and IFN-γ changes were blunted in the T2DM group. Correlation analyses revealed that in T2DM individuals, IL-1β positively correlated with IL-6 and TNF-α both pre- and post-stimulation. IL-6 and IFN-γ showed significant associations with HbA1c and BMI in the non-DM group.

Conclusion:

T2DM group exhibited altered immune patterns marked by heightened IL-1β response and disrupted regulation of IL-6, TNF-α, and IFN-γ, although no statistically significant cytokine differences were observed. These findings suggest an immune dysregulation in T2DM that may contribute to TB susceptibility, warranting further investigation using CD4/CD8-responsive assays in larger, more diverse populations.

Keywords:

chronic inflammation cytokines diabetes mellitus hyperglycemia tuberculosis

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