Effects of topical corticosteroid therapy on Langerhans cell antigen presenting function in human skin.
We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
Ashworth
J
J
Department of Medicine (Dermatology), Charing Cross and Westminster Medical School, London, U.K.
Booker
J
J
Breathnach
S M
SM
D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000502:physiology*; D001623:Betamethasone / Q000627:therapeutic use*; D001624:Betamethasone Valerate / Q000627:therapeutic use; D002990:Clobetasol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006681:HLA-D Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; C010893:clobetasone butyrate; D001623:Betamethasone; D001624:Betamethasone Valerate; D002990:Clobetasol