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Journal of Environmental Toxicology 2002;17(4):325-332.
비장세포의 Th cytokine 생산에 있어서 chlorpyrifos의 영향
Effects of Chlorpyrifos on the Production of Splenic Th Cytokines
Byeong Suk Chae
A helper T(Th)1-mediated response is known to enhance cell-mediated immunity, while a Th2-mediated response is associated with the humoral immunity that is elevated IgE levels and eosinophilia. Prostaglandin (PG)E₂ results in the decreased capability of lymphocytes to produce Th1 cytokines. with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T lymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGE₂ pathway. The purpose of this study is to determine the effect of CPF on the in vitro production of Th cytokines and the role of PGE₂ on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF (0.1, 1, 10 and 100 μM) in the presence or absence of indomethacin or PGE₂ for 12 h and then were incubated with concanavalin (Con) A for 48 h. These reults showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF sjgnificantly increased the splenic IL-4 production at low doses (0.1 and 1 μM) but did not affect at high doses (10 and 100 μM). Indomethacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose-dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 μM. High dose of CPF significantly reduced the PGE₂-decreased production of IL-2 and IFN-γ, while the PGE₂ induced production of IL-4 was significantly enhanced by CPF 1 μM. These findings suggest that CPF may down-regulate the immune response of Th1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Th1 cytokines may not be mediated by endogenous PGE₂. Also, CPF may attenuate the exogenous PGE₂-decreased Th1 immune response in a dose-dependent manner hut may affect dose-independently the PGE₂-induced Th2 immune response.
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