Are cysteinyl leukotrienes involved in allergic responses in human skin?

BACKGROUND: Cysteinyl leukotrienes have been suggested to be involved in producing the symptoms of both the early and late phases of the allergic response in the lung and other tissues. OBJECTIVE: To use scanning laser Doppler imaging, microdialysis and immunocytochemistry to explore the mediator and cellular mechanisms of the dermal allergic response. METHODS: Thirteen atopic volunteers received intradermal injections into the forearm of grass pollen or D. pteronyssinus extract. Changes in dermal blood flow up to 8 h were monitored by scanning laser Doppler imaging. The release of histamine, PGD2 and LTC4/D4/E4 was assessed by dermal microdialysis. Skin biopsies were taken at 6 h to determine numbers of mast cells, eosinophils, basophils, Langerhans' cells, and monocytes/macrophages, and the expression of COX-1, COX-2, 5-LO and FLAP. RESULTS: Allergen provocation produced an immediate weal and flare response followed by an erythematous induration peaking at 6 h. During the first hour, c. 84 pmoles of histamine and c. 0.3 pmoles of PGD2 were recovered by microdialysis (both P < 0.001) but LTC4/D4/E4 was undetectable. No histamine, PGD2 or LTC4/D4/E4 was detectable at later times. Immunocytochemical examination of biopsies taken at 8 h showed increased numbers of eosinophils and basophils and in COX-2, 5-LO and FLAP, but not COX-1. Expression of 5-LO and FLAP was associated primarily with eosinophils. CONCLUSIONS: These findings suggest that inflammatory cells recruited to the site of allergen injection are not activated to release detectable amounts of cysteinyl leukotrienes. Hence, it is unlikely that the late-phase erythematous induration is mediated by this autocoid.