Therapeutic Implications

Reduced glucocorticoid production as a result of a blunted HPA axis response or diminished glucocorticoid sensitivity has been associated with numerous autoimmune/inflammatory diseases, as described above.We have recently described a new mechanism of glucocorticoid resistance related to exposure to the bacterial toxin anthrax lethal toxin. Although we have yet to show the full extent of the involvement of LeTx repression of nuclear hormone receptors in LeTx toxicity, it is reasonable to predict that there may be potential clinical therapeutic implications of LeTx repression of GR. It is clear that a balanced HPA axis and glucocorticoid production is required for survival from LeTx. If other bacterial toxins also induce GR resistance, this could potentially also contribute to their toxicity. This data suggests that care should be taken when treating exposure to LeTx with glucocorticoids (and potentially the anthrax bacterium) as glucocorticoid treatment may not be in the patient's best interest. Identification of the precise mechanism by which LeTx represses GR and other nuclear hormone receptors could provide novel targets for therapy of anthrax and possibly other bacterial toxins.

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