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. 2013 Jul;208(1):159-69.
doi: 10.1093/infdis/jis524. Epub 2012 Oct 8.

Integrated analysis of innate, Th1, Th2, Th17, and regulatory cytokines identifies changes in immune polarisation following treatment of human schistosomiasis

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Integrated analysis of innate, Th1, Th2, Th17, and regulatory cytokines identifies changes in immune polarisation following treatment of human schistosomiasis

Claire D Bourke et al. J Infect Dis. 2013 Jul.

Abstract

Background: Schistosomiasis elicits cross-regulatory immune responses, but it is unclear how antihelminthic treatment affects this balance. This study integrates data on 13 cytokines elicited by 3 schistosome to examine how praziquantel treatment alters immune polarization and whether post-treatment cytokine profiles influence reinfection status.

Methods: Venous blood from 72 Schistosoma haematobium-exposed participants was cultured with schistosome egg, adult worm, and cercaria antigens pre- and 6 weeks post-praziquantel treatment. Innate inflammatory (tumor necrosis factor α [TNF-α], interleukin(IL-)-6, IL-8), Th1 (interferon γ [IFN-γ], IL-2, IL-12p70), Th2 (IL-4, IL-5, IL-13), Th17 (IL-17A, IL-21, IL-23p19), and regulatory (IL-10) cytokines were quantified via enzyme-linked immunosorbent assay. Cytokine data was integrated using nonmetric multidimensional scaling and factor analysis.

Results: Egg-specific cytokine phenotypes became more proinflammatory post-treatment due to increased TNF-α, IL-6, IL-8, IFN-γ, IL-12p70, and IL-23 levels. Post-treatment cercariae-specific responses were also more proinflammatory reflecting elevated IL-8. In contrast, post-treatment adult worm-specific responses were less inflammatory, reflecting lower post-treatment IL-6. A combination of egg-induced IL-6, IL-12p70, IL-21, and IL-23 and adult worm-induced IL-5 and IL-21 post-treatment was associated with reduced reinfection risk 18 months later.

Conclusions: Praziquantel treatment markedly alters polarization of schistosome-specific cytokine responses, and these changes, particularly in response to egg-stage parasites, may promote resistance to reinfection.

Keywords: Human; cytokine; helminth; immune response; praziquantel; schistosomiasis.

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Figures

Figure 1.
Figure 1.
Levels of innate inflammatory (A), Th1 (B), Th2 (C), Th17 (D), and regulatory (E) cytokines elicited by Schistosoma haematobium antigens changed 6 weeks after curative praziquantel treatment. Cytokine responses were assayed in supernatants from 48 hours whole blood cultures stimulated with S. haematobium cercariae (CAP), adult worm (WWH), and egg (SEA) antigens by enzyme-linked immunosorbent assay (CAP, n = 21; WWH, SEA, and unstimulated, n = 72). Mean pretreatment concentrations (ng/mL) are represented by gray circles and post-treatment cytokine responses are represented by black circles. Levels of cytokine present in parallel unstimulated cultures were subtracted from those present in antigen-stimulated cultures for each participant to account for levels of spontaneously produced cytokine. Pretreatment and 6 week post-treatment responses were compared for each antigen by repeated measures analysis of variance. Horizontal bars indicate median values. IFN-γ, interferon γ; IL-2, interleukin 2; IL-4, interleukin 4; IL-5, interleukin 5; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IL-12p70; interleukin 12p70; IL-13, interleukin 13; IL-17A, interleukin 17A; IL-21, interleukin 21; IL-23, interleukin 23; TNF-α, tumor necrosis factor α. *P < .05, **P < .01, ***P < .001.
Figure 2.
Figure 2.
Cytokine profiles elicited by Schistosoma haematobium cercariae (CAP) (A), adult worm (WWH) (B), and egg (SEA) (C) antigens and spontaneous cytokine production (D) differed 6 weeks post-treatment relative to pretreatment responses. Nonmetric multidimensional scaling ordination plots of participants' combined cytokine responses (interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], interleukin 2 [IL-2], interleukin 4 [IL-4], interleukin 5 [IL-5], interleukin 6 [IL-6], interleukin 8 [IL-8], interleukin 10 [IL-10], interleukin 12p70 [IL-12p70], interleukin 13 [IL-13], interleukin 17A [IL-17A], interleukin 21 [IL-21], and interleukin 23 [IL-23]) before (gray triangles) and 6 weeks after treatment (black triangles) plotted according to 2-dimensional spatial axes (CAP, n = 21; WWH, SEA, and unstimulated, n = 72). The proportion of variance in participant cytokine responses attributable to each axis (Pearson's r2) is shown. Axes are labelled according to the cytokines with which they are most strongly correlated (correlation coefficients for these associations provided in Supplementary Table 1). Axis 2 of the WWH-specific cytokine ordination plot was not strongly associated with any of the pre- or post-treatment cytokine responses assayed. Mean within-group differences reflect the total variation between participant cytokine responses before (white diamond) and after (black diamond) treatment.

References

    1. Fenwick A, Savioli L, Engels D, Robert Bergquist N, Todd MH. Drugs for the control of parasitic diseases: current status and development in schistosomiasis. Trends Parasitol. 2003;19:509–15. - PubMed
    1. Kjetland EF, Kurewa EN, Mduluza T, et al. The first community-based report on the effect of genital Schistosoma haematobium infection on female fertility. Fertil Steril. 2010;94:1551–3. - PubMed
    1. Mostafa MH, Sheweita SA, O'Connor PJ. Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev. 1999;12:97–111. - PMC - PubMed
    1. World Health Organization. Preventive chemotherapy in human helminthiasis. Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers. Geneva, Switzerland: WHO; 2006. pp. 1–56.
    1. Tchuem Tchuente LA, Shaw DJ, Polla L, Cioli D, Vercruysse J. Efficacy of praziquantel against Schistosoma haematobium infection in children. Am J of Trop Med and Hyg. 2004;71:778–82. - PubMed

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