Combined effects of mycotoxin mixtures on human T cell function.
Combined effects of mycotoxin mixtures are of major concern due to the widespread occurrence of human exposure to mixtures. Owing to the lack of sufficient mixture data regarding the human immune function, the aim of this study was to specify, evaluate and predict the combined effects of mycotoxin mixtures upon the functional activity of immune cells. Therefore, a well established model for immunotoxic studies using stimulated human peripheral blood mononuclear cells (PBMC) was applied. To predict the combined effect of the mixture the concepts of concentration addition and response addition were used. Comparable to the individual mycotoxins the mixture suppressed the cytokine production in a concentration-dependent manner. The mixture effect was stronger than the effects caused by the toxins applied singly. The response addition concept described the mixture data within their experimental uncertainty. The in vitro test model presented here was practical to detect and quantify combined effects. Low and weak effect concentrations of mycotoxins may cause strong inhibitory effects on immune functions when occurring together. The experimental design using the concepts of concentration addition and response addition was suitable for predicting the combined effects of mycotoxin mixtures in functional in vitro assays.
Tammer
Beate
B
UFZ Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Leipzig, Germany. beate.tammer@ufz.de <beate.tammer@ufz.de>
Lehmann
Irina
I
Nieber
Karen
K
Altenburger
Rolf
R
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005562:Formazans / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009183:Mycotoxins / Q000633:toxicity*; D011042:Poisons / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism
D016207:Cytokines; D004338:Drug Combinations; D005562:Formazans; D009183:Mycotoxins; D011042:Poisons; D013778:Tetrazolium Salts; C079782:MTT formazan