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, PGD(2) and LTC4/D4E4 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 PGD(2) were recovered by microdialysis (both P < 0.001) but LTC4 D-4 /E-4 was undetectable. No histamine, PGD(2) or LTC4 /D-4/E-4 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.