Effect of intradermal injection of methionine-enkephalin on human skin

Methionine-enkephalin (met-enk) detected in monocytes in psoriatic skin can modulate inflammatory processes and keratinocyte differentiation/prolifera tion in vitro. The purpose of the present study was to determine the effect of intradermal injection of met-enk on normal human skin and on the develo pment of a delayed type skin hypersensitivity reaction. In 6 healthy volunt eers, 50 mu l of met-enk (16, 30, and 45 nmol) was injected once in the for earm and the reaction was evaluated clinically and by video-optical recordi ng for 120 min. Compared to vehicle (0.9% saline), met-enk induced a time- and dose-dependent flare reaction, but no significant stimulation of a weal reaction, The flare reaction was maximal after 1 min and disappeared withi n 45 min. Pre-treatment with the antihistamine cetirizine reduced the flare reaction, Furthermore, the effect of met-enk on lymphocyte/monocyte infilt ration and epidermal proliferation in normal skin and on a delayed type ski n hypersensitivity reaction was assessed. Met-enk (45 nmol/50 mu l) was inj ected at 0, 24 and 48 h. In normal skin, met-enk increased the number of de rmal lymphocytes/monocytes (CD3/CD68 positive cells) and the degree of epid ermal proliferation (MIB1-Ki67). In a delayed type hypersensitivity reactio n induced by tuberculin (PPD), the degree of epidermal proliferation and th e number of infiltrating lymphocytes/monocytes were reduced compared to PPD alone. Our study suggests that intradermal injection of met-enk in normal human skin induces an inflammatory reaction that may involve the release of histamine. In contrast, met-enk seems to down-regulate the development of a delayed type skin hypersensitivity reaction. These results may indicate t hat the direction of the effect of the opioid peptide met-enk on human skin depends on the rate of epidermal proliferation and the activity of immunoc ompetent cells.