Abstract

Psoriasis is a clinical conundrum that affects an estimated 1–3% of the world’s population. The psoriatic disease process, characterized by a type 1 cytokine pattern, is supposed to be maintained by a continuing immune response in a “peripheral lymphoid tissue” that forms in lesional skin and is composed of T cells, dendritic cells, and vessels arranged like a T-dependent zone in lymph nodes. Dehydroepiandrosterone (DHEA), produced from dehydroepiandrosterone sulfate (DHEAS) through the enzymatic activity of DHEA-sulfatase, plays a pivotal role in the development
of the type 1 immune response generated in peripheral lymphoid organs. Taken together, it could be reasoned that DHEA-sulfatase inhibitors may have utility in the treatment of psoriasis. Furthermore, the addition of DHEA-sulfatase inhibitors to calcipotriol, which
encourages type 2 immune response, may provide an additive or synergistic inhibition of the type 1 immune response underlying psoriasis. It has been shown that topical application of cholesterol
sulfate in the hairless mouse causes epidermal hyperkeratosis, which can be prevented by co-application of topical cholesterol. Therefore, as the inhibition of conversion of cholesterol sulfate to cholesterol can induce epidermal hyperkeratosis and may thus abbreviate the benefi t obtained by inhibition of DHEAS to DHEA conversion, topical sulfatase inhibitors should preferably be co-applied with topical cholesterol, though it is also possible that the benefi cial immunological effects
of steroid sulfatase inhibitors outweigh their possible hyperkeratosis stimulation. Alternatively, the production of specifi c DHEA-sulfatase inhibitors can resolve the above concern. DHEA-sulfatase inhibitors may prove invaluable in the treatment of psoriasis.

Keywords: Dehydroepiandrosterone - antagonists & inhibitors, Dehydroepiandrosterone - metabolism, Dermatologic Agents - pharmacology, Steryl-Sulfatase - antagonists & inhibitors, Steryl-Sulfatase - metabolism, Calcitriol - pharmacology, Cytokines - physiology, Dehydroepiandrosterone - metabolism, Dermatologic Agents - pharmacology, Drug Interactions, Enzyme Inhibitors - therapeutic use, Mice, Inbred Strains, Models, Biological, Psoriasis - drug therapy, Steryl-Sulfatase - metabolism