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Early specific host response associated with starting effective tuberculosis treatment in an infection controlled placebo controlled mouse study.

den Hertog AL, de Vos AF, Klatser PR, Anthony RM - PLoS ONE (2013)

Bottom Line: Serum was collected prior to and during the first 3 weeks of isoniazid (INH) and rifampicin (RIF) chemotherapy, and levels of 23 selected cytokines/chemokines were measured using a liquid bead array.In infected mice, IFNγ, IP-10, MIG and MCP-1 levels decreased within 7 days of treatment with RIF+INH compared to placebo.Thus, IFNγ, IP-10, MIG and MCP-1 are promising 'Treat-to-Test' targets for the diagnosis of TB and deserve further investigation in a study on human TB suspects.

View Article: PubMed Central - PubMed

Affiliation: Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands.

ABSTRACT
Recently we proposed exploring the potential of treatment stimulated testing as diagnostic method for tuberculosis (TB). An infection controlled placebo controlled mouse study was performed to investigate whether serum cytokine levels changed measurably during the early phase of TB chemotherapy. Serum was collected prior to and during the first 3 weeks of isoniazid (INH) and rifampicin (RIF) chemotherapy, and levels of 23 selected cytokines/chemokines were measured using a liquid bead array. The serum levels of IFNγ, IP-10, MIG, MCP-1, IL-17 and IL-6 were elevated in the TB infected mice compared to non-infected mice at least at 1 time point measured. In infected mice, IFNγ, IP-10, MIG and MCP-1 levels decreased within 7 days of treatment with RIF+INH compared to placebo. Treatment of non-infected mice in the absence of tuberculosis infection had no effect on these cytokines. IL-17 and IL-6 had decreased to baseline in all infected mice prior to the initiation of treatment. This study demonstrates that systemic levels of some cytokines, more specifically IFNγ, IP-10, MIG and MCP-1, rapidly and specifically change upon starting TB chemotherapy only in the presence of infection in a mouse model. Thus, IFNγ, IP-10, MIG and MCP-1 are promising 'Treat-to-Test' targets for the diagnosis of TB and deserve further investigation in a study on human TB suspects.

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Related in: MedlinePlus

Changes in cytokine levels during TB treatment.IFNγ, IP-10, MIG and MCP-1 levels were measured in infected (left hand panels, A, C, E, G) and non-infected (right hand panels, B, D, F, H) mice before (black squares) and after 3, 7, and 21 days of treatment with RIF+INH (open circles) or placebo (black circles). In the infected groups within 7–21 days of treatment with RIF+INH levels of all 4 cytokines were lower compared to placebo treated mice. In the non-infected mice no differences in levels were seen between different treatments or time points. * p<0.05, ** p<0.01, *** p<0.001
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pone-0057997-g003: Changes in cytokine levels during TB treatment.IFNγ, IP-10, MIG and MCP-1 levels were measured in infected (left hand panels, A, C, E, G) and non-infected (right hand panels, B, D, F, H) mice before (black squares) and after 3, 7, and 21 days of treatment with RIF+INH (open circles) or placebo (black circles). In the infected groups within 7–21 days of treatment with RIF+INH levels of all 4 cytokines were lower compared to placebo treated mice. In the non-infected mice no differences in levels were seen between different treatments or time points. * p<0.05, ** p<0.01, *** p<0.001

Mentions: After 7 days, levels of IFNγ, IP-10 and MCP-1 were significantly decreased in the treated versus placebo groups of infected mice (Figure 3A, 3C, 3E). After 21 days, a significant difference was also found for MIG (Figure 3D). No effect of treatment on any of these four cytokines was detected in uninfected mice (Figure 3B, 3D, 3F, 3H). At 21 days after starting treatment, the levels of all 4 cytokines in the infected treated mice were similar to those of both groups of uninfected mice at that time point (Figure 3).


Early specific host response associated with starting effective tuberculosis treatment in an infection controlled placebo controlled mouse study.

den Hertog AL, de Vos AF, Klatser PR, Anthony RM - PLoS ONE (2013)

Changes in cytokine levels during TB treatment.IFNγ, IP-10, MIG and MCP-1 levels were measured in infected (left hand panels, A, C, E, G) and non-infected (right hand panels, B, D, F, H) mice before (black squares) and after 3, 7, and 21 days of treatment with RIF+INH (open circles) or placebo (black circles). In the infected groups within 7–21 days of treatment with RIF+INH levels of all 4 cytokines were lower compared to placebo treated mice. In the non-infected mice no differences in levels were seen between different treatments or time points. * p<0.05, ** p<0.01, *** p<0.001
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585278&req=5

pone-0057997-g003: Changes in cytokine levels during TB treatment.IFNγ, IP-10, MIG and MCP-1 levels were measured in infected (left hand panels, A, C, E, G) and non-infected (right hand panels, B, D, F, H) mice before (black squares) and after 3, 7, and 21 days of treatment with RIF+INH (open circles) or placebo (black circles). In the infected groups within 7–21 days of treatment with RIF+INH levels of all 4 cytokines were lower compared to placebo treated mice. In the non-infected mice no differences in levels were seen between different treatments or time points. * p<0.05, ** p<0.01, *** p<0.001
Mentions: After 7 days, levels of IFNγ, IP-10 and MCP-1 were significantly decreased in the treated versus placebo groups of infected mice (Figure 3A, 3C, 3E). After 21 days, a significant difference was also found for MIG (Figure 3D). No effect of treatment on any of these four cytokines was detected in uninfected mice (Figure 3B, 3D, 3F, 3H). At 21 days after starting treatment, the levels of all 4 cytokines in the infected treated mice were similar to those of both groups of uninfected mice at that time point (Figure 3).

Bottom Line: Serum was collected prior to and during the first 3 weeks of isoniazid (INH) and rifampicin (RIF) chemotherapy, and levels of 23 selected cytokines/chemokines were measured using a liquid bead array.In infected mice, IFNγ, IP-10, MIG and MCP-1 levels decreased within 7 days of treatment with RIF+INH compared to placebo.Thus, IFNγ, IP-10, MIG and MCP-1 are promising 'Treat-to-Test' targets for the diagnosis of TB and deserve further investigation in a study on human TB suspects.

View Article: PubMed Central - PubMed

Affiliation: Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands.

ABSTRACT
Recently we proposed exploring the potential of treatment stimulated testing as diagnostic method for tuberculosis (TB). An infection controlled placebo controlled mouse study was performed to investigate whether serum cytokine levels changed measurably during the early phase of TB chemotherapy. Serum was collected prior to and during the first 3 weeks of isoniazid (INH) and rifampicin (RIF) chemotherapy, and levels of 23 selected cytokines/chemokines were measured using a liquid bead array. The serum levels of IFNγ, IP-10, MIG, MCP-1, IL-17 and IL-6 were elevated in the TB infected mice compared to non-infected mice at least at 1 time point measured. In infected mice, IFNγ, IP-10, MIG and MCP-1 levels decreased within 7 days of treatment with RIF+INH compared to placebo. Treatment of non-infected mice in the absence of tuberculosis infection had no effect on these cytokines. IL-17 and IL-6 had decreased to baseline in all infected mice prior to the initiation of treatment. This study demonstrates that systemic levels of some cytokines, more specifically IFNγ, IP-10, MIG and MCP-1, rapidly and specifically change upon starting TB chemotherapy only in the presence of infection in a mouse model. Thus, IFNγ, IP-10, MIG and MCP-1 are promising 'Treat-to-Test' targets for the diagnosis of TB and deserve further investigation in a study on human TB suspects.

Show MeSH
Related in: MedlinePlus