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Inammation, Vol. 33, No. 5, October 2010 (# 2010) DOI: 10.1007/s10753-010-9188-1
Asthma and Dehydroepiandrosterone (DHEA): Facts and Hypotheses
Alicja Kasperska-Zajac1,2
AbstractDehydroepiandrosterone (DHEA) is considered as an important immunomodulating and anti-inammatory hormone. Despite the continuing interest in DHEA replacement therapy, our knowledge of its effects upon asthma is very limited. DHEA is able to reverse cytokine imbalances associated with asthma, may prevent and attenuate allergic inammation in airways, and does not possess the undesirable side effects of glucocorticoids; therefore, it may be potentially applied in the treatment of asthma. The steroid-sparing effect observed with DHEA clinically could appear especially favorable in asthmatic patients receiving oral treatment and those inhaling high doses of glucocorticoids. In addition, DHEA and its analogs might prove useful in reversing relative glucocorticoids insensitivity in patients with corticosteroid-resistant asthma. In this review we have focused specically on DHEAs role in asthma.
KEY WORDS: dehydroepiandrosterone; asthma.
INTRODUCTION
The dehydroepiandrosterone (DHEA) and its sul-fated ester (DHEAS) are weak androgen steroids, abundantly secreted by adrenal glands and regulated by the adrenocorticotropic hormone. The circulating half-life of DHEA is relatively short and in the blood, DHEA is predominantly present as its biologically inactive precursor-DHEAS, the so-called stored form, which has a half-life of 1020 h. In peripheral tissues, DHEA is converted from DHEAS by sulfatase [1, 2].
The mechanism and biological role of DHEA(S) are unclear. In spite of continuing efforts, the search for specic steroid nuclear receptor for DHEA has not been successful. High-afnity binding sites for DHEA have been described in T cells [3, 4], which were directly related to stimulated IL-2 production [3]. It has been demonstrated that DHEA binds and modulates different membrane- and nuclear-associated proteins including
peroxisome proliferators activated receptor alpha or pregnane X receptor [5]. As DHEA is a biosynthetic precursor of more potent sex steroids, including testosterone and 17 beta-estradiol, it mediates some of its effects indirectly through activation of androgen or estrogen receptors [6]. It has been shown that DHEAS has important immunomodulating and anti-inammatory effects in animals and human [79]. However, their role in immune processes associated with allergy and asthma remains unclear [10, 11].
DHEA AND ASTHMA
Role for DHEA in Th1/Th2 Imbalance and Regulatory T cell Function
Asthma is a chronic immune-mediated disease, characterized by enhanced...