Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantel - PubMed (original) (raw)

Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantel

Claus M Reimert et al. Clin Vaccine Immunol. 2006 May.

Abstract

Eosinophil activity in vivo and in vitro was studied in relation to infection intensities and plasma cytokine profiles of 51 Schistosoma mansoni-infected Ugandan fishermen before treatment and 24 h and 3 weeks posttreatment. Blood eosinophil numbers significantly declined 24 h posttreatment, but significant eosinophilia had developed by 3 weeks posttreatment. Cellular eosinophil cationic protein (ECP) content increased significantly during the transient eosinopenia but was significantly reduced 3 weeks later. No similar reduction in cellular eosinophil protein X (EPX) content was seen. Before treatment, S. mansoni infection intensity was positively correlated with 24-h boosts in plasma interleukin-5 (IL-5) and IL-6 levels, which were in turn negatively correlated with the posttreatment fall in eosinophil numbers. Significant correlations were observed between pretreatment infection intensities and plasma IL-10 and eotaxin levels. Treatment induced significant fluctuations in plasma IL-5, IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), and eotaxin levels. Optimal relative release of ECP and EPX in vitro was detected in S. mansoni soluble egg antigen-stimulated cultures during transient eosinopenia. Our data suggest that blood eosinophils are activated during S. mansoni infection and that treatment induces a burst in released antigens, causing increased production of IL-5, IL-6, IL-10, and eotaxin; a drop in TNF-alpha levels; and a transient sequestration of eosinophils, which leaves fewer degranulated eosinophils in the circulation 24 h posttreatment, followed by the development of eosinophilia 3 weeks later. During these events, it appears that preferential release of ECP occurs in vivo. Moreover, it is possible that infection intensity-dependent levels of plasma IL-10 may be involved in the prevention of treatment-induced anaphylactic reactions.

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Figures

FIG. 1.

FIG. 1.

Pre- and posttreatment blood eosinophil counts, total ECP counts, and total EPX levels in whole blood extracts; cellular content of ECP and EPX; and plasma ECP and EPX levels. The boxes in panels A and B represent the 25th, 50th, and 75th percentile ranges, and the error bars show the ranges of 10th and 90th percentiles. (A) Blood eosinophil counts. *, P = 0.04; §, P = 1.5 × 10−6. (B) Total ECP and EPX counts in whole blood extracts. *, P ≤ 1.0 × 10−12; §, P = 1.0 × 10−8. (C) Cellular content of ECP and EPX (medians). *, P = 0.005; §, P = 0.002. No significant fluctuations in the cellular content of EPX were seen. (D) Plasma ECP and EPX levels (medians). *, P = 0.001; #, P = 0.019; §, P ≤ 0.027.

FIG. 2.

FIG. 2.

Relative release in vitro of ECP and EPX in whole blood cultures stimulated with SWA, SEA, or medium alone. The relative release is calculated as the released amount of ECP and EPX as a percentage of the total content of ECP or EPX extracted from whole blood before the cultures were set up. The boxes represent the 25th, 50th, and 75th percentile ranges, and the error bars illustrate the ranges of the 10th and 90th percentiles. Significant time-dependent release of ECP and EPX was seen in all cultures (P ≤ 2.2 × 10−15 for all). Optimal release of both ECP and EPX was seen in SEA-stimulated cultures from bleed B after 96 h of incubation. For optimal ECP release, the P values were 3.8 × 10−6 and 1.6 × 10−7 (*), respectively, compared to 96-h cultures stimulated with SWA or medium alone. For optimal EPX release, P values were 7.34 × 10−10 and 5.46 × 10−10 (§), compared to 96-h cultures from bleed B stimulated with SWA or medium alone. Levels of significance compared to SEA-stimulated 96-h cultures from bleed A and bleed C are indicated.

FIG. 3.

FIG. 3.

Plasma cytokine levels before treatment (bleed A) and 24 h (bleed B) and 3 weeks (bleed C) after treatment. The boxes represent the 25th, 50th, and 75th percentile ranges, and the error bars illustrate the ranges of the 10th and 90th percentiles. Significant fluctuations as tested by the Friedman ρ test (levels of significance are indicated in the figures) were seen in IL-5, IL-6, TNF-α, IL-10, and eotaxin-1 levels. No significant fluctuations were seen in IL-4, TGF-β, IL-13, IFN-γ, or RANTES levels. For IL-5, a significant increase (bleed A versus bleed B) followed by a significant decline (bleed B versus bleed C) (* and §, P ≤ 5.0 × 10−6) was seen; in addition, a significant decline (P = 0.02) was seen when bleed A was compared with bleed C. For IL-6, a nonsignificant increase (*, P = 0.063), followed by a significant decline (bleed B versus bleed C) (§, P = 0.016), was seen. For TNF-α, a significant decline (*, P = 0.001) was seen. For IL-10, a significant increase (*, P = 0.025) followed by a significant decline (bleed B versus bleed C) (§, P = 0.033) was seen. For eotaxin, a significant decline (bleed B versus bleed C) (*, P = 0.026) was seen.

FIG. 4.

FIG. 4.

Plasma cytokine levels before treatment (bleed A) and 24 h posttreatment (bleed B) in high-eosinophil responders (n = 33; open boxes) and low-eosinophil responders (n = 18; hatched boxes). The boxes represent the 25th, 50th, and 75th percentile ranges, and the error bars show the ranges of the 10th and 90th percentiles.

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