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

Abstract

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 inhibition 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 daily for 21 days (n=10) with 0.05% clobetasol propionate. The other arm served as control. Weal and flare responses were elicited by intradermal injection of 20 microl of 0.3 mM codeine. The areas of the responses were measured using scanning laser Doppler imaging. Microdialysis was used to assess histamine release. Mast cell numbers and tissue histamine content were assessed in 4-mm punch biopsies. Histamine (20 microl of 1 microM 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% respectively (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 histamine release was reduced by 44% (P=0.022). The weal, but not the flare, induced 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 mast cell numbers and tissue histamine content rather than inhibition by corticosteroids of mast cell degranulation.

Figure 1

The effect of clobetasol on weal and flare responses induced by (a) codeine and (b) histamine. Areas of the volar forearm skin were treated for 21 days with either white soft paraffin (control) or 0.05% clobetasol propionate (steroid) before provocation of weal and flare responses by the intradermal injection of codeine (20 μl of 0.3 mM) or histamine (20 μl of 1 μM). Weal (open symbols) and flare (closed symbols) responses were assessed 10 min after provocation.

Figure 2

The effect of clobetasol on codeine-induced histamine release, tissue histamine levels and dermal mast cell numbers. Areas of the volar forearm skin were treated for 21 days with either white soft paraffin (control) or 0.05% clobetasol propionate (steroid). (a) The peak histamine concentration recovered by microdialysis following intradermal injection of codeine (20 μl of 0.3 mM). (b) Tissue histamine levels and (c) mast cell numbers in biopsies taken at 21 days.

Figure 3

The effect of clobetasol on skin thickness. Areas of the volar forearm skin were treated for 21 days with either white soft paraffin (control) or 0.05% clobetasol propionate. Measurements of skin thickness were taken in both arms before (day 0) and at the 21st day of treatment.