Inhibition by glucocorticoids of the mast cell-dependent weal and flare response in human skin in vivo

1 This study examines the relative contributions made by inhibition of mast cell degranulation, reduction of mast cell recruitment and maturation, and lowering the responsiveness of the vasculature to histamine, in the inhibi tion by glucocorticoids of the weal and flare in human skin. 2 One forearm of healthy human volunteers was treated for 24 h (n=6) or dai ly for 21 days (n=10) with 0.05% clobetasol propionate. The other arm serve d as control. Weal and flare responses were elicited by intradermal injecti on of 20 mul of 0.3 mM codeine. The areas of the responses were measured us ing scanning laser Doppler imaging. Microdialysis was used to assess histam ine release. Mast cell numbers and tissue histamine content were assessed i n 4-mm punch biopsies. Histamine (20 mul of 1 muM i.d.) was used to assess the status of the vasculature. 3 No significant effects were seen at 24 h. At 21 days, clobetasol reduced the areas of the codeine-induced weal and flare responses by 59 and 58% res pectively (both P=0.006). Mast cell numbers were reduced by 47%, (P=0.014) and total tissue histamine content by 52% (P=0.006). Codeine-induced histam ine release was reduced by 44% (P=0.022). The weal, but not the flare, indu ced by histamine was significantly inhibited (P=0.019). Echography revealed a 15% thinning of the skin by clobetasol. 4 These results demonstrate that reduction of the weal and flare responses to codeine following clobetasol treatment, results primarily from reduced m ast cell numbers and tissue histamine content rather than inhibition by cor ticosteroids of mast cell degranulation.