Coincident pre-diabetes is associated with dysregulated cytokine responses in pulmonary tuberculosis.

Nathella Pavan Kumar,Vaithilingam V Banurekha,Rathinam Sridhar,Dina Nair,Thomas B Nutman,Subash Babu,Hardy Kornfeld,Katalin Andrea Wilkinson

doi:10.1371/journal.pone.0112108

Abstract

BackgroundCytokines 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.MethodsTo 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).ResultsTB-PDM is characterized by elevated circulating levels of Type 1 (IFNγ, TNFα and IL-2), Type 17 (IL-17A and IL-17F) and other pro-inflammatory (IL-1β, IFNβ and GM-CSF) cytokines. TB-PDM is also characterized by increased systemic levels of Type 2 (IL-5) and regulatory (IL-10 and TGFβ) cytokines. Moreover, TB antigen stimulated whole blood also showed increased levels of pro-inflammatory (IFNγ, TNFα and IL-1β) cytokines as well. However, the cytokines did not exhibit any significant correlation with HbA1C levels or with bacterial burdens.ConclusionOur 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.

Highlights

Pre-diabetes (PDM) or intermediate hyperglycemia is a high risk state for diabetes that is defined by glycemic variables that are higher than normal, but lower than diabetic thresholds [1]
Type 2 DM is one of the major risk factors for the development of active pulmonary tuberculosis (PTB) and this interaction is typically characterized by elevated systemic levels of pro-inflammatory cytokines especially Type 1 and Type 17 cytokines [6,7], cytokines that appear to play an important role in pathogenesis
We focused on a large panel of Type 1, Type 2, Type 17, regulatory and other pro – inflammatory cytokines in plasma and TB antigen-stimulated whole blood from individuals with active TB and coincident PDM (TB-PDM) and compared these to those with active TB but without pre-diabetes (TB-NDM)

Summary

Introduction

Pre-diabetes (PDM) or intermediate hyperglycemia is a high risk state for diabetes that is defined by glycemic variables that are higher than normal, but lower than diabetic thresholds [1]. Type 2 DM is one of the major risk factors for the development of active pulmonary tuberculosis (PTB) and this interaction is typically characterized by elevated systemic levels of pro-inflammatory cytokines especially Type 1 and Type 17 cytokines [6,7], cytokines that appear to play an important role in pathogenesis. In one study from India, a country with extremely high burdens of both TB and DM, it was shown that among newly diagnosed TB patients, 25% had DM while another 25% had PDM, numbers that are in stark contrast to DM and PDM in the general population where the prevalences are 10% and 8%, respectively [8]. The cytokine interactions that characterize PTB coincident with pre-diabetes (PDM) are not known

Methods

Results

Conclusion