Hormones and lupus: defective dehydroepiandrosterone activity induces impaired interleukin-2 activity of T lymphocytes in patients with systemic lupus erythematosus

Abstract

There is strong evidence to implicate the involvement of sex steroid hormones in the pathogenesis of systemic lupus erythematosus (SLE). However, the precise role of an imbalance of circulating sex hormones in the pathogenesis of the disease remains to be fully elucidated. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of normal T cells and that administration of exogenous DHEA or IL-2 via a vaccinia construct to mice with murine lupus dramatically reverses their clinical autoimmune diseases. Thus, it is possible that in patients with SLE, the reported deficiency of IL-2 production is associated with defective DHEA activity. Indeed, we found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels are not simply a reflection of long term corticosteroid treatment, since serum samples drawn at the onset of disease, prior to any corticosteroid treatment also contained low levels of DHEA. In addition, supplementation with DHEA of the in vitro cultures of T cells restored impaired IL-2 production in patients with SLE. Thus, it would be suggested that defects of IL-2 synthesis in patients with SLE are at least in part due to the low DHEA activity in the serum, and that supplementation of DHEA could improve clinical manifestations in patients with SLE.