Release of histamine and tryptase during continuous and interrupted cutaneous challenge with allergen in humans

To help in understanding the patterns of in vivo mediators release in human allergic skin reactions, we have used a skin chamber model to challenge the denuded bases of skin blisters of 11 sensitive subjects with pollen antigens (Ags) and codeine (C), a mast cell degranulator. Challenges were performed either (1) continuously for 6 hours or (2) in an intermitten fashion that is, Ag or C for the first hour, buffer for the next 4 hours, and then Ag or C during the sixth hour. Fluids in the overlying chamber were assayed for levels of the mast cell components, histamine and tryptase. There was peak release of both histamine and tryptase during the first hour of Ag incubation (89±11 ng/ml and 1428±260 ng/ml, respectively). At continuous Ag-challenge sites, there was a plateau of histamine levels (8.0 to 9.5 ng/ml) during the next 4 hours, whereas tryptase levels decreased progressively to baseline levels. Challenge of continuous Ag-incubation sites with C, a mast cell activator, led to another peak release of both histamine and tryptase. At interrupted Ag-challenge sites, histamine levels decreased abruptly, and tryptase levels decreased progressively after the first hour. Rechallenge of such sites with Ag during the sixth hour induced a peak release of histamine but no increase in tryptase levels. Continuous challenge with C for up to 5 hours in other sites induced an initial peak histamine release without a subsequent plateau. However, such a plateau of histamine (but not tryptase) release occurred after an initial C challenge if Ag was subsequently incubated in a continuous fashion. Basophils were not observed in the chamber fluids or in biopsy specimens of the underlying dermis after the sixth hour of continuous Ag challenge but could be observed in small numbers relative to other leukocytes in touch preparations of the dermal surface. We conclude that the low plateau of histamine release during continuous Ag challenge is not due simply to mediator depletion and may be due to infiltrating basophils, although we have not yet convincingly found such cells in these sites at these time periods.