甲苯達唑及槲皮素對鼷鼠廣東血線蟲症炎症反應之影響

廖育正

doi:10.6342/NTU.2006.00727

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甲苯達唑及槲皮素對鼷鼠廣東血線蟲症炎症反應之影響

Effects of Mebendazole and Quercetin on Inflammatory Responses in Murine Angiostrongyliasis

廖育正 , Masters　　Advisor：蘇霩靄　　

英文 DOI： 10.6342/NTU.2006.00727

廣東血線蟲症；甲苯達唑；槲皮素；嗜酸性腦膜腦炎；細胞激素； angiostrongyliasis ； mebendazole ； quercetin ； eosinophilic meningoencephalitis ； cytokine

Abstract │ Reference (146) │ Altmetrics

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Angiostrongylus cantonensis is the major cause of eosinophilic meningoencephalitis in Taiwan and Southeast Asia.  Clinically, anthelmintic treatment is usually not recommended due to concerns about the theoretical neurologic side-effects caused by degenerating worms.  In addition, the efficacy of steroid therapy is also controversial.  In the present study, the efficacy of mebendazole treatment was examined.  Effects of mebendazole treatment on host immune responses were also investigated.  In addition, the anti-inflammatory efficacy of quercetin, a popular flavonoid antiphlogistic, was also evaluated.  BALB/c mice were infected with 30 infective larvae per os and underwent different therapeutic strategies—without any drug treatment, treated with mebendazole only, or treated with mebendazole and quercetin.  Non-infected mice served as negative controls.  Cytokine concentrations in cerebrospinal fluid and peripheral blood were determined through enzyme-linked immunosorbent assay.  Eosinophil counts in CSF as well as worm recovery in brains were also determined under the microscope.  Cytokine mRNA expressions in mouse brains were also investigated using reverse transcriptase-polymerase chain reaction assay.  The results of this study revealed that, with proper timing and dosages of mebendazole treatment, worm recovery rates were reduced about 80-95 %.  The data also showed that instead of raising the expression of IL-4 and eotaxin, which are CSF eosinophilia-related cytokines, mebendazole medication suppressed the expression levels of these cytokines both in protein level and in mRNA level.  Eosinophil counts in CSF were also significantly lowered in the treated mice.  Concomitant administration of mebendazole and quercetin to infected mice did suppress IL-4 and eotaxin production in CSF both in the early and late onset of treatment groups, but the efficacy was not so remarkable as we expected.  Interestingly, IL-5 expression was only detected in a very low level at 14 days post-infection and even undetectable at 21 days post-infection.  These data suggested that anthelmintic treatment to angiostrongyliasis patients might not be as harmful as generally expected.  Furthermore, IL-5 might not be the major factor in the course of this disease.

Reference ( 146 ) 〈TOP〉

Alicata, J. E. 1965. Biology and distribution of the rat lungworm Angiostrongylus cantonensis and its relation to eosinophilic meningitis and other neurological disorders of man and animals. Advances in Parasitology 3:223-248.
連結：
Alicata, J. E. 1969. Present status of Angiostrongylus cantonensis in man and animals in the tropics. The Journal of Tropical Medicine and Hygiene 72:53-63.
連結：
Alicata, J. E. and Brown, R. W. 1962. Observation on method of human infection with Angiostrongylus cantonensis in Tahiti. Canadian Journal of Zoology 40:755-760.
連結：
Ambu, S. and Mak, J. W. 1981. The effect of mebendazole and flubendazole on Angiostrongylus malaysiensis infection in rats. The Southeast Asian Journal of Tropical Medicine and Public Health 12:228-230.
連結：
Aoki, M., Sugaya, H., Ishida, K., and Yoshimura, K. 1998. The role of CD4+ and CD8+ T-cells in host morbidity and innate resistance to Angiostrongylus cantonensis in the mouse. Parasitology Research 84:91-99.
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