Effects of selected herbicides on cytokine production in vitro.
To evaluate possible deleterious effects of commonly used herbicides on leukocytes, cytokine production was selected as a sensitive indicator. After in vitro exposure of human peripheral blood mononuclear cells from normal donors, the production of all 3 cytokines tested--interferon-gamma (a type 1 cytokine), interleukin-5 (a type 2 cytokine) and tumor necrosis factor-alpha (an inflammatory cytokine)--was impaired by up to 70, 50 and 70% respectively in a concentration-dependent manner in cultures exposed to atrazine (0.03-3 microM in 1% dimethylsulfoxide, DMSO). The effect paralleled that seen with dexamethasone, a known immunosuppressive agent. Other pesticides also dissolved in DMSO--mecoprop, simazine or MCPA (each up to 1 microM)--or dissolved in phosphate-buffered saline--diuron (up to 1 microM), isoproturon (up to 3 microM), metoxuron (up to 8 microM) or metamitron (up to 80 microM)--showed no concentration-related effects on cytokine production. There was, however, an inhibition of IFN-gamma and TNF-alpha production by simazine, metoxuron and mecoprop and of all three cytokines tested by diuron. MCPA (0.01 and 0.1 microM) stimulated the production of TNF-alpha. Thus, exposure to herbicides leading to plasma levels in the micromolar range induces imbalance in cytokine production.
Hooghe
R J
RJ
Environmental Toxicology, Flemish Institute for Technological Research (VITO), Mol, Belgium. rhooghe@farc.vub.ac.be
Devos
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Hooghe-Peters
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D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016895:Culture Media, Serum-Free; D016207:Cytokines; D006540:Herbicides; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma