Effect of Standard Tuberculosis Treatment on Plasma Cytokine Levels in Patients with Active Pulmonary Tuberculosis

Abstract

BackgroundSputum 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.MethodsTwenty-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.ResultsPlasma 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.ConclusionsThese 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.

Circulating Biomarkers of Pulmonary and Extrapulmonary Tuberculosis in Children

“…However, our findings did not reveal any significant differences in the expression levels of these factors in TB-infected children compared to those in control children. Since VEGF in particular has been shown to be a useful biomarker in adult TB (36,37), our findings suggest that more studies are needed on VEGF expression patterns before the utility of VEGF can be universally applied.…”

Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers

“…Multiple studies have demonstrated that there is a measurable and consistent response related to TB disease severity and or the effect of therapy [83][84][85][86][87][88]. Early evidence suggests that these responses will be informative before culture or microscopic conversion is currently detected [78,79,89,90].…”

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

“…[94] From these studies a number of promising markers have been selected, a notable example is IP-10/CXCL-10, a chemokine involved in the establishment of a proinflammatory Th1 response. TB is associated with increased serum IP-10 levels [93,[95][96][97], and at completion of therapy, levels are significantly lower than before treatment/at diagnosis. [64,98,99] This decrease is also measurable in the first weeks of therapy, [63,93] and therefore measurement of the kinetics of this cytokine during treatment may provide useful information on whether patients are responding to the prescribed drugs.…”