Evaluation of immunotoxicity induced by pirimiphos-methyl in male Balb/c mice following exposure to for 28 days.
Pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate: POM) is widely used organophosphorous (OP) insecticide as a grain protectant to control insects during storage. This study was carried out to assess the immunologic effects of POM in Balb/c mice after 28-day oral exposure. Three dose levels of POM (10, 60, or 120 mg/kg/day) were administered orally to mice for 4 weeks. At autopsy after 28-day exposure, there were significant decreases in relative spleen weight and splenic cellularity found at 120 mg POM, but body weight, relative thymic weight, thymic cellularity, and splenic and thymic subsets were not affected. T cell proliferation response induced by Con A was significantly decreased at all dosages though no statistical differences were observed in splenic B cell proliferation. Significant increases in the production of cytokines (IL-2, IL-4, IL-6, IFN-gamma, and IL-10) were evident on the whole, but the increase in production of inflammatory cytokines overwhelmed that of the T(H)1 cell suppressive cytokine (IL-10). The relative levels of three types of autoantibodies, anti-dsDNA, anti-histone, and antinuclear antibody (ANA) were dose-dependently decreased in serum. Oral exposure to POM induced a significant decrease in Immunoglobulin M production capability in Balb/c mice. This decrease in antibody production capability may result from disturbances in cytokine balance produced by splenic immune cells. These results show that POM may induce allergic responses by relatively enhancing T(H)2 development and additionally contribute to chronic inflammation by attracting macrophage by IFN-gamma.
Kim
Hyung Soo
HS
Immunotoxicology Division, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Republic of Korea. kim_hs@kfda.go.kr
Eom
Juno H
JH
Cho
Hye-young
HY
Cho
Young Joo
YJ
Kim
Ji Young
JY
Lee
Jong Kwon
JK
Kim
Seung-Hee
SH
Park
Kui Lea
KL
D000284:Administration, Oral; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007075:Immunoglobulin M / Q000378:metabolism*; D007306:Insecticides / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects*; D015854:Up-Regulation
D001323:Autoantibodies; D016207:Cytokines; D007075:Immunoglobulin M; D007306:Insecticides; D009946:Organothiophosphorus Compounds; C014153:pirimiphos methyl