Replacement therapy of DHEA plus glucocorticoids as substitutes of adrenal hormones during chronic inflammatory diseases

Journal/Book: Z Rheumatol 1999; 58: 306. 1999;

Abstract: R. H. Straub; Klinik und Poliklinik für Innere Medizin I Klinikum der Universität Regensburg A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis was found in animal models with chronic inflammatory diseases and the defect was located in more central portions of the HPA axis. This defect of neuroendocrine regulatory mechanisms may contribute to the onset or the chronicity of the model disease. Since these first observations in animal models were made evidence has accumulated that the possible defect in the HPA axis in humans is more distal to the hypothalamus or pituitary: 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) was significantly lower after ACTH stimulation in patients with rheumatoid arthritis 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 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 which confirmed an earlier study in mice. Since IL-6 is an important factor for B lymphocyte differentiation the missing downregulation of this cytokine and others such as TNF may be a significant risk factor in rheumatic diseases. ... le

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