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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 systemic levels of Type 1, Type 2 and other pro-inflammatory and regulatory cytokines in TB-PDM.The plasma levels of Type 1 (IFNγ, TNFα, IL-2); Type 17 (IL-17A, IL-17F and IL-22) cytokines (A) and Type 2 (IL-4, IL-5, IL-13); regulatory (IL-10 and TGFβ) cytokines (B) and other pro-inflammatory (IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12 and GM-CSF) were measured by ELISA in TB-PDM (n = 48) and TB-NDM (n = 42) 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-g001: Elevated systemic levels of Type 1, Type 2 and other pro-inflammatory and regulatory cytokines in TB-PDM.The plasma levels of Type 1 (IFNγ, TNFα, IL-2); Type 17 (IL-17A, IL-17F and IL-22) cytokines (A) and Type 2 (IL-4, IL-5, IL-13); regulatory (IL-10 and TGFβ) cytokines (B) and other pro-inflammatory (IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12 and GM-CSF) were measured by ELISA in TB-PDM (n = 48) and TB-NDM (n = 42) 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 Type 1 and Type 17 cytokines in active PTB, we measured the circulating levels of IFN-γ, TNFα and IL-2 as well as IL-17A, IL-17F and IL-22 in TB-PDM and TB-NDM individuals (Figure 1). As shown in Figure 1A, the systemic levels of all three Type 1 cytokines – IFNγ (Geometric Mean of 335.9 pg/ml in TB-PDM versus 169.2 pg/ml in TB-NDM), TNFα (GM of 338.4 pg/ml vs. 252.4 pg/ml) and IL-2 (GM of 25.1 pg/ml vs. 13.9 pg/ml) were significantly higher in TB-PDM compared to TB-NDM individuals. Similarly, the systemic levels of the prototypical Type 17 cytokines – IL-17A (GM of 106.3 pg/ml vs. 90.6 pg/ml) and IL-17F (GM of 202.8 pg/ml vs. 138.1 pg/ml) were also significantly higher in TB-PDM compared to TB-NDM individuals. In contrast, no significant differences in IL-22 levels were found between the two groups. Thus, TB-PDM is associated with heightened levels of Type 1 and Type 17 at the time of presentation of active PTB.


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 systemic levels of Type 1, Type 2 and other pro-inflammatory and regulatory cytokines in TB-PDM.The plasma levels of Type 1 (IFNγ, TNFα, IL-2); Type 17 (IL-17A, IL-17F and IL-22) cytokines (A) and Type 2 (IL-4, IL-5, IL-13); regulatory (IL-10 and TGFβ) cytokines (B) and other pro-inflammatory (IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12 and GM-CSF) were measured by ELISA in TB-PDM (n = 48) and TB-NDM (n = 42) 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-g001: Elevated systemic levels of Type 1, Type 2 and other pro-inflammatory and regulatory cytokines in TB-PDM.The plasma levels of Type 1 (IFNγ, TNFα, IL-2); Type 17 (IL-17A, IL-17F and IL-22) cytokines (A) and Type 2 (IL-4, IL-5, IL-13); regulatory (IL-10 and TGFβ) cytokines (B) and other pro-inflammatory (IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12 and GM-CSF) were measured by ELISA in TB-PDM (n = 48) and TB-NDM (n = 42) 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 Type 1 and Type 17 cytokines in active PTB, we measured the circulating levels of IFN-γ, TNFα and IL-2 as well as IL-17A, IL-17F and IL-22 in TB-PDM and TB-NDM individuals (Figure 1). As shown in Figure 1A, the systemic levels of all three Type 1 cytokines – IFNγ (Geometric Mean of 335.9 pg/ml in TB-PDM versus 169.2 pg/ml in TB-NDM), TNFα (GM of 338.4 pg/ml vs. 252.4 pg/ml) and IL-2 (GM of 25.1 pg/ml vs. 13.9 pg/ml) were significantly higher in TB-PDM compared to TB-NDM individuals. Similarly, the systemic levels of the prototypical Type 17 cytokines – IL-17A (GM of 106.3 pg/ml vs. 90.6 pg/ml) and IL-17F (GM of 202.8 pg/ml vs. 138.1 pg/ml) were also significantly higher in TB-PDM compared to TB-NDM individuals. In contrast, no significant differences in IL-22 levels were found between the two groups. Thus, TB-PDM is associated with heightened levels of Type 1 and Type 17 at the time of presentation of active PTB.

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