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KMID : 0893320020170040325
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Journal of Environmental Toxicology
2002 Volume.17 No. 4 p.325 ~ p.332
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Effects of Chlorpyrifos on the Production of Splenic Th Cytokines
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Chae Byeong-Suk
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Abstract
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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 if elevated IgE levels and eosinophilia. Prostaglandin (PG)Eresults in the decreased capability of Iymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T Iymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGEpathway. The purpose of this study is to determine the effort of CPF on the in vitro production of Th cytokines and the role of PGEon the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF(0.1, 1, 10 and 100M) in the presence of absence of indomethacin or PGEfor 12 h and then were incubated with concanavalin (Con) A for 48 h. These results showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the splenic IL-4 production at low doses (0.1 and 1M) but did not affect at high doses (10 and 100 M). 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 M. High dose of CPF significantly reduced the PGE-decreased production of IL-2 and IFN-γ, while the PGE- induced production of IL-4 was significantly enhanced by CPF 1 M. These findings suggest that CPF nay down-regulate the immune response of Th 1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Thl cytokines may not be mediated by endogenous PGE. Also, CPF may attenuate the exogenous PGE-decreased Th 1 immune response in a dose--dependent manner but may affect dose-independently the PGE-induced Th2 immune response.
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KEYWORD
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Chlorpyrifos, Indomethacin, IL-2, IFN -, IL -4, PGE
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