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Effect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis.

Riou C, Perez Peixoto B, Roberts L, Ronacher K, Walzl G, Manca C, Rustomjee R, Mthiyane T, Fallows D, Gray CM, Kaplan G - PLoS ONE (2012)

Bottom Line: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status.By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02).No significant changes were observed in other studied immune mediators.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, Institute of Infectious Diseases and Molecular Medicine (IIDMM), Clinical Laboratory Sciences, University of Cape Town, Cape Town, Western Cape, South Africa.

ABSTRACT

Background: Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy.

Methods: Twenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion.

Results: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators.

Conclusions: These data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.

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Related in: MedlinePlus

Comparison of the decrease rate of IP-10 and VEGF in TB+HIV− and TB+HIV+ individuals upon TB therapy. (A) Longitudinal plasma IP-10 and VEGF concentrations before, during and after TB therapy in TB+HIV− (Red) and TB+HIV+ (Black) individuals. Values were log-transformed. Median values with 95% CI for TB+HIV− (n = 20) and TB+ HIV+ (n = 22) individuals are depicted in red and black, respectively. A shaded grey box represents the duration of TB therapy. Statistical analyses were performed using random-effects linear regression. (B) Comparison of fold-changes in plasma IP-10 and VEGF concentrations between baseline and 26-week measurements (end of TB therapy) in TB+HIV− and TB+HIV+ subjects. Each dot represents one individual. Open circles correspond to individuals who presented with sputum conversion at ≤8 weeks, closed circles correspond to individuals who presented with sputum culture conversion between 12 and 26 weeks after TB therapy initiation and crosses identify individuals where sputum culture conversion occurred after 26 weeks post treatment. Doted lines depict 50% and 80% reduction of cytokine expression levels. Statistical analyses were performed using non-parametric Mann-Whitney U test.
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pone-0036886-g004: Comparison of the decrease rate of IP-10 and VEGF in TB+HIV− and TB+HIV+ individuals upon TB therapy. (A) Longitudinal plasma IP-10 and VEGF concentrations before, during and after TB therapy in TB+HIV− (Red) and TB+HIV+ (Black) individuals. Values were log-transformed. Median values with 95% CI for TB+HIV− (n = 20) and TB+ HIV+ (n = 22) individuals are depicted in red and black, respectively. A shaded grey box represents the duration of TB therapy. Statistical analyses were performed using random-effects linear regression. (B) Comparison of fold-changes in plasma IP-10 and VEGF concentrations between baseline and 26-week measurements (end of TB therapy) in TB+HIV− and TB+HIV+ subjects. Each dot represents one individual. Open circles correspond to individuals who presented with sputum conversion at ≤8 weeks, closed circles correspond to individuals who presented with sputum culture conversion between 12 and 26 weeks after TB therapy initiation and crosses identify individuals where sputum culture conversion occurred after 26 weeks post treatment. Doted lines depict 50% and 80% reduction of cytokine expression levels. Statistical analyses were performed using non-parametric Mann-Whitney U test.

Mentions: To further characterize TB treatment-induced down-regulation of plasma concentrations of IP-10 and VEGF, we compared the kinetics of IP-10 and VEGF levels between TB+HIV− and TB+HIV+ individuals. In both groups, IP-10 and VEGF down-regulation followed a one-phase decay curve (Figure 4A). Upon TB therapy, the rate of decline in IP-10 level, between baseline and 26-week measurements, was significantly steeper in TB+HIV− patients when compared with TB+HIV+ patients (p = 0.02); where the median fold changes in IP-10 concentrations were 0.24 (IQR: 0.08–0.37) in TB+HIV− subjects and 0.41 (IQR: 0.23–0.67) in TB+HIV+ subjects (Figure 4B). Of note, fold changes in IP-10 concentrations between TB+HIV− and TB+HIV+ individuals were also significantly different between baseline and 2, 4, 52 and 78 weeks post TB therapy initiation [p = 0.03, p = 0.019, p = 0.012 and p = 0.045, respectively (data not shown)]. In contrast, the rate of decline in VEGF concentrations were comparable for both groups (Figure 4A), with no differences being apparent in the median fold changes between baseline and 26 week for either patient group (Figure 4B).


Effect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis.

Riou C, Perez Peixoto B, Roberts L, Ronacher K, Walzl G, Manca C, Rustomjee R, Mthiyane T, Fallows D, Gray CM, Kaplan G - PLoS ONE (2012)

Comparison of the decrease rate of IP-10 and VEGF in TB+HIV− and TB+HIV+ individuals upon TB therapy. (A) Longitudinal plasma IP-10 and VEGF concentrations before, during and after TB therapy in TB+HIV− (Red) and TB+HIV+ (Black) individuals. Values were log-transformed. Median values with 95% CI for TB+HIV− (n = 20) and TB+ HIV+ (n = 22) individuals are depicted in red and black, respectively. A shaded grey box represents the duration of TB therapy. Statistical analyses were performed using random-effects linear regression. (B) Comparison of fold-changes in plasma IP-10 and VEGF concentrations between baseline and 26-week measurements (end of TB therapy) in TB+HIV− and TB+HIV+ subjects. Each dot represents one individual. Open circles correspond to individuals who presented with sputum conversion at ≤8 weeks, closed circles correspond to individuals who presented with sputum culture conversion between 12 and 26 weeks after TB therapy initiation and crosses identify individuals where sputum culture conversion occurred after 26 weeks post treatment. Doted lines depict 50% and 80% reduction of cytokine expression levels. Statistical analyses were performed using non-parametric Mann-Whitney U test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3351475&req=5

pone-0036886-g004: Comparison of the decrease rate of IP-10 and VEGF in TB+HIV− and TB+HIV+ individuals upon TB therapy. (A) Longitudinal plasma IP-10 and VEGF concentrations before, during and after TB therapy in TB+HIV− (Red) and TB+HIV+ (Black) individuals. Values were log-transformed. Median values with 95% CI for TB+HIV− (n = 20) and TB+ HIV+ (n = 22) individuals are depicted in red and black, respectively. A shaded grey box represents the duration of TB therapy. Statistical analyses were performed using random-effects linear regression. (B) Comparison of fold-changes in plasma IP-10 and VEGF concentrations between baseline and 26-week measurements (end of TB therapy) in TB+HIV− and TB+HIV+ subjects. Each dot represents one individual. Open circles correspond to individuals who presented with sputum conversion at ≤8 weeks, closed circles correspond to individuals who presented with sputum culture conversion between 12 and 26 weeks after TB therapy initiation and crosses identify individuals where sputum culture conversion occurred after 26 weeks post treatment. Doted lines depict 50% and 80% reduction of cytokine expression levels. Statistical analyses were performed using non-parametric Mann-Whitney U test.
Mentions: To further characterize TB treatment-induced down-regulation of plasma concentrations of IP-10 and VEGF, we compared the kinetics of IP-10 and VEGF levels between TB+HIV− and TB+HIV+ individuals. In both groups, IP-10 and VEGF down-regulation followed a one-phase decay curve (Figure 4A). Upon TB therapy, the rate of decline in IP-10 level, between baseline and 26-week measurements, was significantly steeper in TB+HIV− patients when compared with TB+HIV+ patients (p = 0.02); where the median fold changes in IP-10 concentrations were 0.24 (IQR: 0.08–0.37) in TB+HIV− subjects and 0.41 (IQR: 0.23–0.67) in TB+HIV+ subjects (Figure 4B). Of note, fold changes in IP-10 concentrations between TB+HIV− and TB+HIV+ individuals were also significantly different between baseline and 2, 4, 52 and 78 weeks post TB therapy initiation [p = 0.03, p = 0.019, p = 0.012 and p = 0.045, respectively (data not shown)]. In contrast, the rate of decline in VEGF concentrations were comparable for both groups (Figure 4A), with no differences being apparent in the median fold changes between baseline and 26 week for either patient group (Figure 4B).

Bottom Line: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status.By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02).No significant changes were observed in other studied immune mediators.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, Institute of Infectious Diseases and Molecular Medicine (IIDMM), Clinical Laboratory Sciences, University of Cape Town, Cape Town, Western Cape, South Africa.

ABSTRACT

Background: Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy.

Methods: Twenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion.

Results: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators.

Conclusions: These data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.

Show MeSH
Related in: MedlinePlus