Coincident Pre-Diabetes Is Associated with Dysregulated Cytokine Responses in Pulmonary Tuberculosis

Background: Cytokines play an important role in the pathogenesis of pulmonary tuberculosis (PTB) - Type 2 diabetes mellitus co-morbidity. However, the cytokine interactions that characterize PTB coincident with pre-diabetes (PDM) are not known. Methods: To identify the influence of coincident PDM on cytokine levels in PTB, we examined circulating levels of a panel of cytokines in the plasma of individuals with TB-PDM and compared them with those without PDM (TB-NDM). Results: TB-PDM is characterized by elevated circulating levels of Type 1 (IFN gamma, TNF alpha and IL-2), Type 17 (IL-17A and IL-17F) and other pro-inflammatory (IL-1 beta, IFN beta and GM-CSF) cytokines. TB-PDM is also characterized by increased systemic levels of Type 2 (IL-5) and regulatory (IL-10 and TGF beta) cytokines. Moreover, TB antigen stimulated whole blood also showed increased levels of pro-inflammatory (IFN gamma, TNF alpha and IL-1 beta) cytokines as well. However, the cytokines did not exhibit any significant correlation with HbA1C levels or with bacterial burdens. Conclusion: Our data reveal that pre-diabetes in PTB individuals is characterized by heightened cytokine responsiveness, indicating that a balanced pro and anti - inflammatory cytokine milieu is a feature of pre-diabetes -TB co-morbidity.