Effect in Man of Anti‐Allergic Drugs on the Immediate and Late Phase Cutaneous Allergic Reactions Induced by Anti‐IgE

Abstract

Wheal and flare reactions as well as a late cutaneous allergic reaction (LCAR) were induced by anti-human IgE in healthy subjects. The effect of the beta 2-adrenoceptor stimulant terbutaline, the histamine-1 (H1) receptor blocking agent mepyramine and the synthetic glucocorticoid betamethasone on these reactions was studied. All administrations were given intradermally (i.d.). The immediate reaction to anti-IgE was inhibited by 3 micrograms terbutaline and 30 micrograms mepyramine (P less than 0.01) whereas 50 micrograms betamethasone had no effects. Terbutaline had no effect on the flare response induced by i.d. injected histamine but a slight effect on whealing. Terbutaline and mepyramine weakly reduced the LCAR throughout the observation period of 24 h (P less than 0.01). In contrast, betamethasone almost completely abolished the LCAR. It is concluded that the two phases of the skin reaction to anti-IgE are interrelated since an inhibition of the early phase was followed by an attenuation of the LCAR. The mechanism of action of steroids seems to differ fundamentally from that of other anti-allergic drugs since inhibition of the early step in the reaction is not essential to the action on the late step. It is further suggested that terbutaline inhibits anti-IgE-mediated cutaneous reactions by inhibition of the mast cell release reaction.

Mast Cells, Tissue Histamine and Eosinophils in Early- and Late-Phase Skin Reactions: Effects of a Single Dose of Prednisolone

“…This is in harmony with other studies which also report the lack of effect by prednisolone on weal and flare responses elicited by other challenge agents such as compound 48/80 or histamine [11,12]. Since only a limited number of the subjects in the present study exhibited a visual late phase, we cannot deter mine whether the present dose of prednisolone also inhibits the symptomatic expression of a dermal late phase as has been reported previously [13], although there was an inhibition of the local eosinophil influx.…”

Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions.

“…Both studies found increased wheal reactions in the late evening when serum cortisol levels are low. In the majority ofhuman studies, however, pharmacological doses of steroids do not appear to influence immediate mast cell responses (30)(31)(32)(33)(34). A recent study by Vichyanond and Nelson (35) and experiments reported here failed to detect diurnal variation in early phase responses after cutaneous antigen challenge.…”

Characterization of IgE-mediated cutaneous immediate and late-phase reactions in nonallergic horses

“…This reaction has been used in humans to evaluate the effects of drugs on IgE-mediated reactions. [10][11][12][13][14][15][16] In dogs, a model of allergic dermatitis has been successfully developed by the use of anti-IgE. 8,9 To our knowledge, such a model of allergic dermatitis in horses has not been developed.…”

“…Researchers have effectively developed models of cutaneous allergic inflammation in other species, including dogs 8,9 and humans. [10][11][12][13][14][15][16] Briefly, allergic skin disease is often mediated by type I hypersensitivity reactions. These reactions (immediate and late-phase hypersensitivity) are initiated by antigen exposure.…”