Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production.
Mycotoxins are a structurally diverse group of secondary metabolites produced by different genera of fungi, and include deoxynivalenol (DON), T-2 toxin, aflatoxin B1 (AFB1) and fumonisin B1 (FB1). Despite widespread human exposure and potent immunomodulation in animals, their effects on the human immune system remain to be defined. In this study, the effect of these toxins on human lymphocyte proliferation was evaluated using the MTT assay. Additionally, the effect of DON on cytokine profiles was measured. A 50% inhibition in cell proliferation was observed with a DON concentration of 216 ng/ml. T-2 toxin was more potent with 50% inhibition between 1 and 5 ng/ml. Negligible effects were observed with AFB1 and FB1, and a mixture of DON with either FB1 or AFB1 did not show any synergistic effects in this assay. Short-term treatment of PHA-stimulated lymphocytes with DON (100, 200 and 400 ng/ml) modulated the kinetics of IL-2, IL-4 and IL-6 production. IL-2 levels were up to 12-fold higher (P<0.05) in comparison to control levels at toxin concentrations of 200 and 400 ng/ml 72 h after treatment. IL-4 levels were only slightly elevated and IL-6 levels were slightly inhibited by these DON concentrations. The kinetics of cytokine production was followed for an extended period of 8-9 days at DON concentrations of 200 and 400 ng/ml. At the lower DON concentration (200 ng/ml), IL-2 levels were elevated 17-25-fold with a concomitant mild elevation in IFN-gamma. Consistent with earlier experiments, IL-6 levels were slightly suppressed by DON at this concentration. At 400 ng/ml, IL-2 levels were again significantly (P<0.05) elevated until 6 days post-treatment, while the effects on IL-4 and IL-6 were less marked. These data suggest DON has potent effects on human lymphocyte cytokine production which merit investigation in exposed human populations.
Meky
F A
FA
Molecular Epidemiology Unit, Epidemiology and Health Services Research, Algernon Firth Building, School of Medicine, University of Leeds, LS2 9JT, Leeds, UK.
Hardie
L J
LJ
Evans
S W
SW
Wild
C P
CP
D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014255:Trichothecenes / Q000009:adverse effects*
D015850:Interleukin-6; D014255:Trichothecenes; D015847:Interleukin-4; C007262:deoxynivalenol