Decrease in Enkephalin Levels in Psoriatic Lesions after Calcipotriol and Mometasone Furoate Treatment

Abstract

Background: Enkephalins are opioid peptides that can modulate immune responses and inflammatory processes. Furthermore, they inhibit keratinocyte proliferation/differentiation in vitro. Previously, we have shown that enkephalins are present in increased amounts in lesional psoriasis. Objective: To determine the effect of topical treatment with the vitamin D analogue calcipotriol and the corticosteroid mometasone furoate on the level of methionine-enkephalin (enk) in psoriatic lesions. Methods: Twelve psoriatic patients were treated with calcipotriol and mometasone furoate for 14 days without or with hydrocolloid occlusion. Keratome biopsies were obtained from treated and untreated skin, and the extracted enk was quantified by radioimmunoassay. Furthermore, punch biopsies were obtained for immunohistochemical analysis. Results: Clinically, both calcipotriol and mometasone furoate improved psoriasis to the same degree, the effects being more pronounced after occlusion. Histologically, treatment with mometasone furoate without occlusion decreased both the epidermal thickness/parakeratosis and the number of dermal immunocompetent cells (CD3- and CD68-positive cells). In contrast, treatment with calcipotriol without occlusion reduced the epidermal thickness and the degree of parakeratosis but decreased the number of CD3- and CD68-positive cells only slightly. The mean enk level was decreased by 26 and 86% by calcipotriol without and with occlusion and by 16 and 63% by mometasone furoate without and with occlusion, respectively. The decreases in the enk levels corresponded to the degree of clinical improvement but not to the histological changes. Conclusion: The increased levels of enk in psoriatic lesions are reduced in parallel with the clinical improvement induced by a topical vitamin D analogue and a corticosteroid. Because enkephalins can modulate epidermal differentiation and inflammatory processes, the findings indicate that enkephalins may play a role in the pathogenesis of psoriasis.

Regulated Proenkephalin Expression in Human Skin and Cultured Skin Cells

“…This is consistent with a previous report on increased expression of enkephalin antigens in this disease (Nissen et al ., 1999). This diffuse pattern also appears to be consistent with the opinion that a pathologically hyperactive epidermal/immune response to bacterial superantigens is an important mechanism in the etiology of psoriasis (Travers et al ., 2001).…”

“…Proopiomelanocortin-derived β-endorphin, one of their endogenous ligands (Bigliardi-Qi et al ., 2000, 2004; Kauser et al ., 2003, 2004; Tobin, 2006), is locally produced in the skin (Slominski et al ., 1992, 1993; Furkert et al ., 1997; Slominski, 1998) and stimulates epidermal and follicular melanogenesis (Kauser et al ., 2003, 2004). Although there are reports demonstrating the presence of Met-enkephalin antigen in adult mammalian skin (Weihe et al ., 1983; Chew and Leung, 1991; Zagon et al ., 1996; Nissen et al ., 1999), there is a shortage of information on local proenkephalin gene expression and its relationship to skin pathology and the environmental regulation of proenkephalin (PENK) expression.…”

Opioidergic Signaling—A Neglected, Yet Potentially Important Player in Atopic Dermatitis

“…This seems to be particularly interesting, since in another study, 12 psoriatic patients were treated topically with calcipotriol ointment (50 µg/g twice a day), mometasone furoate ointment (0.1%), or appropriate vehicles for 14 days. As expected, both treatments improved the clinical symptoms and the histological findings (reduction in epidermal thickness as well as in the degree of parakeratosis; minor improvement in the number of CD3+ and CD68+ cells) [135]. Moreover, the level of cutaneous Met-enkephalin (OGF) was significantly decreased by both treatments [135].…”

The opioid growth factor, [Met5]‐enkephalin, inhibits DNA synthesis during recornification of mouse tail skin

“…epidermolytic hyperkeratosis, ichthyosiform erythroderma, Vohlwinkel's syndrome). In light of recent reports of elevated [Met 5 ]-enkephalin levels in psoriatic lesions , Nissen et al 1999, it is reasonable to postulate that OGFr may be absent, present in low number or non-functional in this and other pathologic states of epidermal hyperplasia with suspected psychogenic basis (e.g. exfoliative dermatitis, lichen planus, eczemas).…”