Cytokine and antibody production during the course of resolution in Plasmodium yoelii 17XL-infected BALB/c mice treated with febrifugine and isofebrifugine mixture from leaves of Hydrangea macrophylla var. Otaksa

Ishih, Akira; Nagata, Toshi; Kobayashi, Fuminori; Miyase, Toshio; Terada, Mamoru

doi:10.1007/s00436-004-1187-4

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…Doses of 10 mg/kg of febrifugine had previously been associated with toxicity and subsequent mortality of mice [15]. However, a 5-day oral dosage of 1 mg/kg of the febrifugine and isofebrifugine mixture showed parasite clearance and no mouse mortality [16]. In the present study, autopsy of mice treated with bud-extracts showed gross hepatotoxicity (data not shown).…”

Section: In Vivo Antimalarial Testmentioning

confidence: 50%

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of Hydrangea macrophylla var. Otaksa, with special reference to its antimalarial activity

et al. 2006

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Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using highperformance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16-0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent-febrifugine and isofebrifugine mixture-in H. macrophylla var. Otaksa is both part-and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.

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Section: In Vivo Antimalarial Testmentioning

confidence: 50%

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of Hydrangea macrophylla var. Otaksa, with special reference to its antimalarial activity

et al. 2006

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“…In a nonlethal P. yoelii infection, IgG2 was previously reported to be predominant, although both IgG1 and IgG3 were present during the primary infection (Langhorne et al 1984). As for fatal malaria infections in mice, the low burden of parasites induced by drug treatment may trigger a production of protective parasite-specific antibodies which clear all parasites from peripheral blood at the later phase of infection (Ishih et al 2004;Langhorne et al 1989;Stevenson and Tam 1993). In the present study, the titers of the parasite-specific IgG1 and IgG2a of the infected 129S1 mice elevated significantly from day 15 pi; elevations which were corresponding with the onset of decrease in parasitemia.…”

Section: Discussionmentioning

confidence: 95%

The course of a primary infection of Plasmodium yoelii 17XL in both 129S1 and IFN-γ receptor-deficient mice

2012

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In the present study, we found that 129S1 mice are resistant to the infection with Plasmodium yoelii 17XL, which is highly virulent and causes lethal infection in various strains of mice. In contrast, IFN-γ receptor-deficient (IFN-γR(-/-)) mice on the 129S1 background were much more susceptible than 129S1 mice with intraperitoneal infection with 1 × 10(5) parasitized erythrocytes. The mortality in 129S1 and IFN-γR(-/-) mice was 11.6 and 79.4 %, respectively. Following inoculation of the parasites, both 129S1 and IFN-γR(-/-) mice showed a progressive increase in parasitemia. Growth rate of malaria parasites at the early stages of infection in the IFN-γR(-/-) mice was faster than that in 129S1 mice, and this difference in growth rate might cause the earlier death of IFN-γR(-/-) host from day 8 of infection than that of 129S1. In surviving mice of both strains, however, malaria parasites in their bloodstream began to decrease in number right after a peak of parasitemia and were not detectable by a microscopic examination during the observation period. Next, we investigated the cytokine and antibody production in 129S1 and IFN-γR(-/-) mice during infection. An analysis of cytokines showed that serum IFN-γ and IL-4 levels elevated significantly from day 1 and day 4 of infection, respectively, in both 129S1 and IFN-γR(-/-) mice when compared with the levels from the uninfected controls. Following the infection, significantly higher levels of malaria-specific IgG1 and IgG2a antibodies in the infected 129S1 mice were detected from day 15, and these elevations were coincident with the decrease of parasitemia. On the other hand, the levels of malaria-specific antibodies in IFN-γR(-/-) mice had a tendency to elevate on day 21 but did not reach statistical significance. The present data indicate that IFN-γR plays an essential role in mediating the early immune mechanisms induced by the infection of erythrocytic stages of P. yoelii 17XL parasite, leading to host survival.

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Outcome of primary lethal and nonlethal Plasmodium yoelii malaria infection in BALB/c and IFN-γ receptor-deficient mice following chloroquine treatment

et al. 2012

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IFN-γ receptor-deficient (IFN-γR(-/-)) mice and control wild-type (WT) mice, with or without chloroquine (CQ) treatment, were infected intraperitoneally with Plasmodium yoelii 17XL (lethal) and P. yoelii 17XNL (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. Without CQ treatment, both IFN-γR(-/-) and WT mice were susceptible to infection showing 100 % mortality after infection with 1 × 10(5) P. yoelii 17XL-parasitized erythrocytes. The P. yoelii 17XL-infected WT mice could survive by CQ treatment at a dose of 20 mg/kg for 3 days from day 3 postinfection (pi). Malaria parasites in their bloodstream could not be detected in the surviving mice after day 13 pi. CQ treatment, however, could not rescue IFN-γR(-/-) mice infected with P. yoelii 17XL. Next, we examined the production of the parasite-specific antibodies in P. yoelii 17XL-infected, CQ-treated mice. Although the production of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies was observed on days 14 and 28 pi in WT mouse sera, only IgG1 was detected on day 28 pi in IFN-γR(-/-) mouse sera. On the other hand, in the nonlethal P. yoelii 17XNL infection, WT mice could control a primary infection with 1 × 10(5) parasitized erythrocytes. Although IFN-γR(-/-) mice could not control and died with increasing parasitemia, the mice could survive by CQ treatment. Both WT and IFN-γR(-/-) mice with and without medication, which survived from P. yoelii 17XNL infection, showed the variable levels of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies during the course of infection. The present data indicate that the IFN-γ receptors are needed to control the infection and parasite-specific IgG2a antibody plays an essential role in recovery from the infection of erythrocytic stages of P. yoelii 17XL or P. yoelii 17XNL parasite.

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Cytokine and antibody production during the course of resolution in Plasmodium yoelii 17XL-infected BALB/c mice treated with febrifugine and isofebrifugine mixture from leaves of Hydrangea macrophylla var. Otaksa

Cited by 5 publications

References 22 publications

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of Hydrangea macrophylla var. Otaksa, with special reference to its antimalarial activity

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of Hydrangea macrophylla var. Otaksa, with special reference to its antimalarial activity

The course of a primary infection of Plasmodium yoelii 17XL in both 129S1 and IFN-γ receptor-deficient mice

Outcome of primary lethal and nonlethal Plasmodium yoelii malaria infection in BALB/c and IFN-γ receptor-deficient mice following chloroquine treatment

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