Carbofuran suppresses T-cell-mediated immune responses by the suppression of T-cell responsiveness, the differential inhibition of cytokine production, and NO production in macrophages

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Title
Carbofuran suppresses T-cell-mediated immune responses by the suppression of T-cell responsiveness, the differential inhibition of cytokine production, and NO production in macrophages
Author(s)
Sun Duck Jeon; Jong Seok Lim; Chang Kiu Moon
Bibliographic Citation
Toxicology Letters, vol. 119, no. 2, pp. 143-155
Publication Year
2001
Abstract
The effects of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzo-furanol N-methylcarbamate) on the functions of T cells in splenocytes and peritoneal macrophages were examined in view of T-cell-mediated immune response (CMIR) in male C57BL/6 mice. Intraperitoneal administration of carbofuran (0.075, 0.15 and 0.3 mg/kg body weight) resulted in significant suppression of delayed type hypersensitivity (DTH), indicating that it caused the suppression of CMIR. Carbofuran decreased Concanavalin A (Con A)- and alloantigen-induced proliferation, and interleukin (IL)-2 production of splenocytes. In vitro addition of rIL-2 could not completely restore the suppressed T-cell proliferation, and IL-2-induced proliferation of Con A-activated splenocytes was also suppressed, which implied that carbofuran caused defects in IL-2 production and responsiveness of splenocytes to IL-2, leading to the suppression of T-cell proliferation. Con A-induced production of interferon-γ (IFN-γ) was significantly suppressed by carbofuran, while that of IL-4 was not affected. The production of transforming growth factor-β from splenocytes was also significantly inhibited by carbofuran. Judging from these results, carbofuran might directly suppress the cytokine production in T helper 1 (Th1) cells. In addition, IFN-γ-induced production of nitric oxide (NO) in macrophages was also inhibited by carbofuran, which might be one of the important mechanisms of carbofuran-induced CMIR suppression in mice. Collectively, the present study suggests that carbofuran might suppress CMIR through the suppression of T-cell responsiveness, IFN-γ production in Th1 cells, and NO generation in macrophages.
Keyword
carbofurancell-mediated immune responsesdelayed type hypersensitivitysplenocytesmixed lymphocyte reactioncytokinesnitric oxidemacrophages
ISSN
0378-4274
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0378-4274(00)00307-6
Type
Article
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1. Journal Articles > Journal Articles
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