The Th1-Promoting Effects of Dehydroepiandrosterone Can Provide An Explanation For the Stronger Th1-Immune Response of Women

Estrogens foster immunological processes driven bycd4+ th2 cells and b cells and androgens foster th1cd4+ and cd8+ cell activity. higher levels of ifngammaand il-2 and lower levels of il-4 and il-10 aredetected in the phytohemagglutinin-stimulatedlymphocyte culture supernatants of men compared withwomen. it is documented that the physiologic levels ofestrogens produced during the luteal phase of themenstrual cycle shift the female immune system toward ath2-type response and that the th1 cytokines areincreased in postmenopausal women. however, the th1immune response is also surprisingly stronger in women,hence affording them a better protection againstinfections. nickel sensitivity, a th1 immune reaction,seems to be more common in women even if men wearearrings. further, not only the th2 but also the th1autoimmune diseases are generally more common inwomen than men. how do women advance a stronger th1response than men? it is suggested that in contrast to theparadigm that estrogens lead to a th2 bias, estrogens canenhance th1 cytokine production also. however, thediscrepant effects of estrogens are difficult to bereconciled from a molecular viewpoint and hence are notadvocated by all authors. this paper provides anexplanation: the effects of dehydroepiandrosterone on th1/th2 balance seem to be model-specific; in humansdehydroepiandrosterone, represents a pivotal up-regulatorof th1 immune response. steroid sulphatase is amicrosomal enzyme that cleaves the sulphate group ofdehydroepiandrosterone sulphate. this enzyme iscontrolled by an x-linked gene that escapes the lyoneffect of x-inactivation; as a result, women usually haveabout twice steroid sulphatase in their cells, includingmacrophages, as have men. putting all these facts together,it could be concluded that women’s macrophages, whichcontain higher steroid sulphatase levels and enterperipheral lymphoid organs through afferent lymphaticdrainage, produce higher levels ofdehydroepiandrosterone in these organs; and higher levelsof this hormone produce stronger th1 immune responses.