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Background: The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of T-helper 2[interleukin (IL)-4 and IL-5] cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines [IL-33, IL-25 and thymic stromal lymphopoietin (TSLP)],released through innate immune mechanisms, may play a role in pathogenesis.

Objectives: To identify Th2-initiating cytokines in lesional and nonlesional skinfrom patients with CSU and to compare the results with a control group.

Methods: Paired biopsies (one from a 4–8 h spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects,and studied by immunohistochemistry and confocal microscopy.

Results: There were increases in IL-4+and IL-5+cells in lesional skin vs. controls(P=0.03 andP<0.001, respectively) and marked elevations in the numbers ofIL-33+, IL-25+and TSLP+cells in the dermis of lesional skin vs. both nonlesional skin (P=0.002,P=0
01 and P=0.04, respectively) and controls (P=0.001,P<0.001 andP=0.005, respectively). There was also a correlation between the numbers of IL-33+and IL-25+cells (r=0.808,P=0.015). IL-33 localized to CD31+endothelial cells, CD90+fibroblasts, CD68+macrophages and tryptase+mast cells, whereas IL-25 was expressed by epithelial cells, mast cells and major basic protein-positive eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and patients with CSU.

Conclusions: Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways might play a role in the mechanism of wealing. AsTh2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these findings may also have therapeutic implications.