Allergen-induced histamine release in intact human skin in vivo assessed by skin microdialysis technique: Characterization of factors influencing histamine releasability

Background: The purposes of the study were to characterize allergen-induced histamine release in intact human skin in vivo by using a novel microdialysis technique and to study covariates influencing histamine releasability. Methods: Hollow microdialysis fibers were inserted in to the upper dermis in 15 timothy-sensitive subjects. Up to 12 fibers were inserted in each subject. Each fiber was perfused with Krebs-Ringer's solution at a rate of 3.0 mu l/min. Three to four serial dilutions of allergen were applied to the skin by intracutaneous injections or skin prick test above individual fibers. Samples were collected in two 2-minute fractions before skin challenge and in 10 consecutive samples for 20 minutes after skin challenge. Histamine was assayed spectrofluorometrically. Results: A significant dose-response relationship for histamine release was demonstrated with intracutaneous tests and skin prick tests. The time to reach peak histamine release after an intracutaneous test was 4 to 8 minutes, compared with 12 to 14 minutes for a skin prick test. Histamine release correlated significantly with wheal size. Intrasubject coefficient of variation on histamine release was about 20%. A substantial intersubject variation in histamine releasability was observed. Seventy to seventy-five percent of the variation could be accounted for by a combination of gender, total and allergen-specific IgE, and an in vitro basophil histamine release test. Conclusion: Using a skin microdialysis technique, we have described in detail histamine release in intact human skin by allergen. The microdialysis method proved to be a reproducible technique for monitoring histamine release in allergic skin reactions and for studying histamine releasability of skin mast cells in vivo.