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-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-gamma (IFN-gamma) was significantly suppressed by carbofuran, while that of IL-4 was not affected. The production of transforming growth factor-beta 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-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. Collectively, 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.
Jeon
S D
SD
College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, 151-742, Seoul, South Korea.
Lim
J S
JS
Moon
C K
CK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002235:Carbofuran / Q000627:therapeutic use / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007111:Immunity, Cellular / Q000187:drug effects; D007306:Insecticides / Q000627:therapeutic use / Q000633:toxicity; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007519:Isoantigens / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D007306:Insecticides; D007376:Interleukin-2; D007519:Isoantigens; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D002235:Carbofuran