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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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Correlation between plasma VEGF concentrations at 2 weeks post TB therapy initiation and time to sputum culture conversion.(A) TB+HIV− individuals; (B) TB+HIV+ individuals. VEGF concentration values were log-transformed. Statistical associations were performed by a two-tailed non-parametric Spearman rank correlation.
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pone-0036886-g005: Correlation between plasma VEGF concentrations at 2 weeks post TB therapy initiation and time to sputum culture conversion.(A) TB+HIV− individuals; (B) TB+HIV+ individuals. VEGF concentration values were log-transformed. Statistical associations were performed by a two-tailed non-parametric Spearman rank correlation.

Mentions: We next analyzed if any measured plasma factor could be potential candidates as surrogate markers for sputum culture conversion. Cytokine concentrations, at each time point, were correlated with the time to sputum culture conversion in TB+HIV− and TB+HIV+ individuals. Figure 5 shows that plasma VEGF concentrations, measured at 2 weeks after initiation of TB treatment, was positively associated with the time of sputum culture conversion in TB+HIV− individuals (r = 0.72, p = 0.0017, Figure 5A). Positive associations were also observed between VEGF concentrations measured at 4, 12, and 26 weeks post TB treatment and time of sputum culture conversion [p = 0.0032, p = 0.043 and p = 0.0036, respectively (data not shown)]. Of note, no association was found between baseline VEGF concentrations and the time of culture sputum conversion. These associations were not observed in the TB+HIV+ group at any time point (Figure 5B). Moreover, no associations were observed between any other cytokine measured and time of culture sputum conversion. These data suggest that plasma VEGF concentrations, measured as early as 2 weeks after the initiation of TB treatment, could predict bacterial clearance in HIV negative individuals and could be used as a prospective marker of time to sputum culture conversion.


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)

Correlation between plasma VEGF concentrations at 2 weeks post TB therapy initiation and time to sputum culture conversion.(A) TB+HIV− individuals; (B) TB+HIV+ individuals. VEGF concentration values were log-transformed. Statistical associations were performed by a two-tailed non-parametric Spearman rank correlation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351475&req=5

pone-0036886-g005: Correlation between plasma VEGF concentrations at 2 weeks post TB therapy initiation and time to sputum culture conversion.(A) TB+HIV− individuals; (B) TB+HIV+ individuals. VEGF concentration values were log-transformed. Statistical associations were performed by a two-tailed non-parametric Spearman rank correlation.
Mentions: We next analyzed if any measured plasma factor could be potential candidates as surrogate markers for sputum culture conversion. Cytokine concentrations, at each time point, were correlated with the time to sputum culture conversion in TB+HIV− and TB+HIV+ individuals. Figure 5 shows that plasma VEGF concentrations, measured at 2 weeks after initiation of TB treatment, was positively associated with the time of sputum culture conversion in TB+HIV− individuals (r = 0.72, p = 0.0017, Figure 5A). Positive associations were also observed between VEGF concentrations measured at 4, 12, and 26 weeks post TB treatment and time of sputum culture conversion [p = 0.0032, p = 0.043 and p = 0.0036, respectively (data not shown)]. Of note, no association was found between baseline VEGF concentrations and the time of culture sputum conversion. These associations were not observed in the TB+HIV+ group at any time point (Figure 5B). Moreover, no associations were observed between any other cytokine measured and time of culture sputum conversion. These data suggest that plasma VEGF concentrations, measured as early as 2 weeks after the initiation of TB treatment, could predict bacterial clearance in HIV negative individuals and could be used as a prospective marker of time to sputum culture conversion.

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