Upregulation of TNF-alpha and IL-3 expression in lesional and uninvolved skin in different types of urticaria

Background: Although mast cells are known to secrete a broad spectrum of pr oinflammatory and immunomodulatory cytokines, the role of these molecules i n mast cell-dependent cutaneous inflammation is not clear. Objective: We decided to study biopsy specimens from lesional and nonlesion al skin of patients with acute, chronic recurrent, delayed pressure, and co ld urticaria; from fleeting wheals of prick test reactions to allergens; an d from normal skin of nonallergic subjects. Methods: Cryostat sections were stained by immunohistochemistry with antibo dies against IL-3, IL-8, TNF-alpha, and mast cell-specific tryptase. In ser ial sections with tryptase and each cytokine, reactivity of mast cells was studied as well. Results: Compared with normal skin and prick test reactions, immunoreactivi ty for TNF-alpha and IL-3 was significantly increased on endothelial and pe rivascular cells of the upper dermis in all urticaria lesions, In nonlesion al skin comparable upregulation was noted on endothelial cells and for TNF- alpha on perivascular cells of patients with delayed pressure urticaria. In addition, TNF-alpha was expressed throughout the epidermis in lesional and nonlesional skin of patients with all types of urticaria, but not in norma l control subjects. Sequential biopsy specimens from patients with cold urt icaria shelved upregulation of TNF-alpha and IL-3 on endothelial cells 30 m inutes after elicitation of lesions with an ice cube. In contrast to these findings, epidermal immunoreactivity, as well as endothelial and perivascul ar cell expression of IL-8, were only slightly altered in urticaria compare d with normal skin. In sequentially stained sections, few tryptase-positive mast cells reacted to TNF-alpha, few reacted to IL-3 in pressure urticaria only, and practically none stained for IL-8. Conclusion: These findings suggest that the cytokines studied here are invo lved in the pathology of urticaria, possibly by inducing subthreshold infla mmation in endothelial cells of uninvolved skin.