DHEA & inflammatory diseases.

[Guest guest]

Hi all

Thought this was kinda interesting with it's connection of DHEA and inflammatory

diseases. Sorry for the length.

Dee~

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Z Rheumatol 2000;59 Suppl 2:II/108-18

Replacement therapy with DHEA plus corticosteroids in patients with chronic

inflammatory diseases--substitutes of adrenal and sex hormones.

Straub RH, Scholmerich J, Zietz B.

In chronic inflammatory diseases, such as rheumatoid arthritis, an alteration of

the HPA stress response results in inappropriately low cortisol secretion in

relation to adrenocorticotropic hormone (ACTH) secretion.

Furthermore, it has recently been shown that the serum levels of another adrenal

hormone, dehydroepiandrosterone (DHEA), were significantly lower after ACTH

stimulation in patients with rheumatoid arthritis without prior corticosteroids

than in healthy controls. These studies clearly indicate that 'chronic

inflammation' alters, particularly, the adrenal response. However, at this

point, the reason for the specific alteration of adrenal function in relation to

pituitary function remains to be determined.

Since one of the down-regulated adrenal hormones, DHEA, is an inhibitor of

cytokines due to an inhibition of nuclear factor-kappa B (NF-kappa

activation, low levels of this hormone may be deleterious in chronic

inflammatory diseases.

We have recently demonstrated that DHEA is a potent inhibitor of IL-6.

Since IL-6 is an important factor for B lymphocyte differentiation, the missing

down-regulation of this cytokine, and others such as TNF, may be a significant

risk factor in rheumatic diseases. Since in these patients, administration of

prednisolone or the chronic inflammatory process itself alters adrenal function,

endogenous adrenal hormones in relation to proinflammatory cytokines change.

Furthermore, these mechanisms may also lead to shifts in steroidogenesis which

have been demonstrated in chronic inflammatory diseases.

It was repeatedly demonstrated that the serum level of the sulphated form of

DHEA (DHEAS) was significantly lower in patients with chronic inflammatory

diseases.

Since DHEAS is the pool for peripheral sex steroids, such as testosterone and 17

beta-estradiol, lack of this hormone leads to a significant sex hormone

deficiency in the periphery.

This overview will demonstrate mechanisms why DHEAS is reduced in chronic

inflammatory diseases.

As a consequence, we suggest a 'combined' therapy with corticosteroids 'plus'

DHEA in chronic inflammatory diseases.