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

The effects of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzo-furanol N-methy lcarbamate) on the functions of T cells in splenocytes and peritoneal macro phages were examined in view of T-cell-mediated immune response (CMIR) in m ale 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 C MIR. Carbofuran decreased Concanavalin A (Con A)- and alloantigen-induced p roliferation, and interleukin (IL)-2 production of splenocytes. In vitro ad dition of rIL-2 could not completely restore the suppressed T-cell prolifer ation, and IL-2-induced proliferation of Con A-activated splenocytes was al so suppressed, which implied that carbofuran caused defects in IL-2 product ion and responsiveness of splenocytes to IL-2, leading to the suppression o f T-cell proliferation. Con A-induced production of interferon-gamma (IFN-g amma) was significantly suppressed by carbofuran, while that of IL-4 was no t affected. The production of transforming growth factor-beta from splenocy tes was also significantly inhibited by carbofuran. Judging from these resu lts, carbofuran might directly suppress the cytokine production in T helper 1 (Th1) cells. In addition, IFN-gamma -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. C ollectively, the present study suggests that carbofuran might suppress CMIR through the suppression of T-cell responsiveness, IFN-gamma production in Th1 cells, and NO generation in macrophages. (C) 2001 Elsevier Science Irel and Ltd. All rights reserved.