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Experimental Biology and Medicine 226:1051-1060 (2001)
© 2001 Society for Experimental Biology and Medicine


ORIGINAL ARTICLE

Stimulation of Th2 Response by High Doses of Dehydroepiandrosterone in KLH-Primed Splenocytes

Caigan Du1,*, Qiunong Guan{dagger}, M. Wahid Khalil{dagger} and Subramaniam Sriram*

* Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, Tennessee 37212; and
{dagger} Lawson Research Institute, St. Joseph's Care Center and Department of Medicine, Pharmacology, and Toxicology, University of Western Ontario, London, Ontario N6A 4V2, Canada

Although dehydroepiandrosterone (DHEA) has long been considered as a precursor for steroid hormones, it has also been shown to have regulatory effects in immune homeostasis. We have examined the effect of high DHEA doses on T cell proliferation, differentiation, and cytokine secretion patterns following stimulation with mitogens and soluble antigens. DHEA profoundly inhibited T cell receptor-mediated T cell proliferation in the upstream of IL-2R signaling. Addition of DHEA to KLH-primed splenocytes stimulated Th2 response, indicated by an increase of IL-4 or a decrease of IFN-{gamma} production in the cultures. Further studies showed that DHEA enhanced IL-4, but inhibited IL-12-mediated T cell proliferation and IL-12 production in antigen-presenting cells (APCs). Our data demonstrated that supraphysiologic levels of DHEA favored Th2 immune responses in vitro by inhibition of IL-12 production from APCs and/or stimulation of Th2 proliferation during the interactions of T cells with APCs.

Key Words: DHEA • T lymphocytes • Th1 • Th2







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