The mycotoxins citrinin, gliotoxin, and patulin affect interferon-gamma rather

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1: Environ Toxicol. 2002;17(3):211-8.

The mycotoxins citrinin, gliotoxin, and patulin affect interferon-

gamma rather than interleukin-4 production in human blood cells.

Wichmann G, Herbarth O, Lehmann I.

UFZ Centre for Environmental Research Leipzig-Halle, Department of

Human Exposure Research and Epidemiology, Permoser Strasse 15,

Germany. guwich@...

Exposure to molds diminishes the numbers of T-helper type 1 (Th1)

cells in the peripheral blood of children and is a risk factor for

the development of allergic diseases (results of LARS: Leipzig

Allergy Risk Children Study, Mueller et al. 2002). We hypothesized

that mycotoxins are responsible for this effect and therefore

investigated the influence of citrinin, gliotoxin, and patulin on

human peripheral blood mononuclear cells (PBMC). CD3/CD28-stimulated

PBMC of healthy donors were incubated for 24 h with the mycotoxins

in serial dilutions and triplicates. Vitality and proliferation were

tested using the MTT assay and T-cell function by the expression of

cytokines (ELISA, intracellular cytokine staining, and real-time

polymerase chain reaction (RT-PCR) for interferon-gamma (IFN-gamma)

and interleukin-4 (IL-4). The cytokine secretion was inhibited at

concentrations 2-130 times lower compared to vitality (ELISA versus

MTT assay). The strongest inhibition of cytokine expression was

found for IFN-gamma: 8.3 microg/mL citrinin, 34.2 ng/mL gliotoxin,

and 64.8 ng/mL patulin caused a 50% inhibition of the IFN-gamma

release (50% inhibitory dose, ID(50)). For IL-4 release the

corresponding ID(50) values were 21.6 microg/mL citrinin, 82.8 ng/mL

gliotoxin, and 243.2 ng/mL patulin. Furthermore, 3 ng/mL patulin

caused a significant increase of IL-4 but a significant suppression

of IFN-gamma. On the mRNA level, after 24 h an unaltered or enhanced

IL-4 was observed compared to a reduced IFN-gamma expression. Using

a method of intracellular cytokine staining, we were able to show

that the described effects are caused by a reduction of the number

of IFN-gamma-producing T lymphocytes rather than by a reduced

functional capacity of the single cell. We suggest that mycotoxins

primarily cause stronger inhibition of IFN-gamma-producing Th1

cells, which may lead to T-cell polarization toward the Th2

phenotype and may raise the risk for the development of allergies.

Copyright 2002 Wiley Periodicals, Inc.

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