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

Kumar NP, Banurekha VV, Nair D, Sridhar R, Kornfeld H, Nutman TB, Babu S - PLoS ONE (2014)

Bottom Line: 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).TB-PDM is also characterized by increased systemic levels of Type 2 (IL-5) and regulatory (IL-10 and TGFβ) cytokines.However, the cytokines did not exhibit any significant correlation with HbA1C levels or with bacterial burdens.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.

ABSTRACT

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 (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.

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.

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Related in: MedlinePlus

Elevated TB antigen stimulated and unstimulated levels of IFNγ, TNFα, IL-17A and IL-1β in TB-PDM.The unstimulated (A) or TB antigen stimulated (B) levels of IFNγ, TNFα, IL-17A and IL-1β were measured by ELISA in whole blood of a subset of TB-PDM (n = 22) and TB-NDM (n = 22) individuals. The data are represented as scatter plots with each circle representing a single individual (light grey – PDM and dark grey – NDM). P values were calculated using the Mann-Whitney test.
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pone-0112108-g002: Elevated TB antigen stimulated and unstimulated levels of IFNγ, TNFα, IL-17A and IL-1β in TB-PDM.The unstimulated (A) or TB antigen stimulated (B) levels of IFNγ, TNFα, IL-17A and IL-1β were measured by ELISA in whole blood of a subset of TB-PDM (n = 22) and TB-NDM (n = 22) individuals. The data are represented as scatter plots with each circle representing a single individual (light grey – PDM and dark grey – NDM). P values were calculated using the Mann-Whitney test.

Mentions: To determine the influence of PDM on TB antigen stimulated cytokine production in active PTB, we measured circulating levels of these cytokines following stimulation of whole blood with no antigen or a cocktail of TB antigens (ESAT-6, CFP-10, TB 7.7) in a subset (n = 22 each) of TB-PDM and TB-NDM individuals (Figure 2). As shown in Figure 2A, the spontaneously produced levels of the IFNγ (GM of 70.1 pg/ml vs. 34.8 pg/ml), TNFα (GM of 69.7 pg/ml vs. 35.6 pg/ml) and IL-1β (GM of 64.4 pg/ml vs. 44.5 pg/ml) were significantly higher in TB-PDM compared to TB-NDM individuals. Similarly, as shown in Figure 2B, the TB antigen stimulated levels of IFNγ (GM of 278.8 pg/ml vs. 120.1 pg/ml), TNFα (GM of 67.2 pg/ml vs. 42.5 pg/ml) and IL-1β (GM of 65.9 pg/ml vs. 43.1 pg/ml) were also significantly higher in TB-PDM compared to TB-NDM individuals. Thus, TB-PDM is associated with heightened levels of TB antigen stimulated pro-inflammatory cytokines.


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

Kumar NP, Banurekha VV, Nair D, Sridhar R, Kornfeld H, Nutman TB, Babu S - PLoS ONE (2014)

Elevated TB antigen stimulated and unstimulated levels of IFNγ, TNFα, IL-17A and IL-1β in TB-PDM.The unstimulated (A) or TB antigen stimulated (B) levels of IFNγ, TNFα, IL-17A and IL-1β were measured by ELISA in whole blood of a subset of TB-PDM (n = 22) and TB-NDM (n = 22) individuals. The data are represented as scatter plots with each circle representing a single individual (light grey – PDM and dark grey – NDM). P values were calculated using the Mann-Whitney test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230980&req=5

pone-0112108-g002: Elevated TB antigen stimulated and unstimulated levels of IFNγ, TNFα, IL-17A and IL-1β in TB-PDM.The unstimulated (A) or TB antigen stimulated (B) levels of IFNγ, TNFα, IL-17A and IL-1β were measured by ELISA in whole blood of a subset of TB-PDM (n = 22) and TB-NDM (n = 22) individuals. The data are represented as scatter plots with each circle representing a single individual (light grey – PDM and dark grey – NDM). P values were calculated using the Mann-Whitney test.
Mentions: To determine the influence of PDM on TB antigen stimulated cytokine production in active PTB, we measured circulating levels of these cytokines following stimulation of whole blood with no antigen or a cocktail of TB antigens (ESAT-6, CFP-10, TB 7.7) in a subset (n = 22 each) of TB-PDM and TB-NDM individuals (Figure 2). As shown in Figure 2A, the spontaneously produced levels of the IFNγ (GM of 70.1 pg/ml vs. 34.8 pg/ml), TNFα (GM of 69.7 pg/ml vs. 35.6 pg/ml) and IL-1β (GM of 64.4 pg/ml vs. 44.5 pg/ml) were significantly higher in TB-PDM compared to TB-NDM individuals. Similarly, as shown in Figure 2B, the TB antigen stimulated levels of IFNγ (GM of 278.8 pg/ml vs. 120.1 pg/ml), TNFα (GM of 67.2 pg/ml vs. 42.5 pg/ml) and IL-1β (GM of 65.9 pg/ml vs. 43.1 pg/ml) were also significantly higher in TB-PDM compared to TB-NDM individuals. Thus, TB-PDM is associated with heightened levels of TB antigen stimulated pro-inflammatory cytokines.

Bottom Line: 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).TB-PDM is also characterized by increased systemic levels of Type 2 (IL-5) and regulatory (IL-10 and TGFβ) cytokines.However, the cytokines did not exhibit any significant correlation with HbA1C levels or with bacterial burdens.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.

ABSTRACT

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 (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.

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.

Show MeSH
Related in: MedlinePlus