Immunotoxicity of one trichothecene

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J Toxicol Environ Health. 1996 May;48(1):1-34.

Toxicology of deoxynivalenol (vomitoxin).

Rotter BA, Prelusky DB, Pestka JJ.

Centre for Food and Animal Research,

Agriculture and Agri-Food Canada, Ottawa, Ontario, Canada.

Trichothecene mycotoxins are a group of structurally similar fungal

metabolites that are capable of producing a wide range of toxic

effects. Deoxynivalenol (DON, vomitoxin), a trichothecene, is

prevalent worldwide in crops used for food and feed production,

including in Canada and the United States. Although DON is one of the

least acutely toxic trichothecenes, it should be treated as an

important food safety issue because it is a very common contaminant of

grain. This review focuses on the ability of DON to induce toxicologic

and immunotoxic effects in a variety of cell systems and animal

species. At the cellular level, the main toxic effect is inhibition of

protein synthesis via binding to the ribosome. In animals, moderate to

low ingestion of toxin can cause a number of as yet poorly defined

effects associated with reduced performance and immune function. The

main overt effect at low dietary concentrations appears to be a

reduction in food consumption (anorexia), while higher doses induce

vomiting (emesis). DON is known to alter brain neurochemicals. The

serotoninergic system appears to play a role in mediation of the

feeding behavior and emetic response. Animals fed low to moderate

doses are able to recover from initial weight losses, while higher

doses induce more long-term changes in feeding behavior. At low

dosages of DON, hematological, clinical, and immunological changes are

also transitory and decrease as compensatory/adaptation mechanisms are

established. Swine are more sensitive to DON than mice, poultry, and

ruminants, in part because of differences in metabolism of DON, with

males being more sensitive than females. The capacity of DON to alter

normal immune function has been of particular interest. There is

extensive evidence that DON can be immunosuppressive or

immunostimulatory, depending upon the dose and duration of exposure.

While immunosuppression can be explained by the inhibition of

translation, immunostimulation can be related to interference with

normal regulatory mechanisms. In vivo, DON suppresses normal immune

response to pathogens and simultaneously induces autoimmune-like

effects which are similar to human immunoglobulin A (IgA) nephropathy.

Other effects include superinduction of cytokine production by T

helper cells (in vitro) and activation of macrophages and T cells to

produce a proinflammatory cytokine wave that is analogous to that

found in lipopolysaccharide-induced shock (in vivo). To what extent

the elevation of cytokines contributes to metabolic effects such as

decreased feed intake remains to be established. Although these

effects have been largely characterized in the mouse, several

investigations with DON suggest that immunotoxic effects are also

likely in domestic animals. Further toxicology studies and an

assessment of the potential of DON to be an etiologic agent in human

disease are warranted.