Epidermal cytokines in contact hypersensitivity: Immunological roles and practical applications.
Local trauma and topical exposure to sensitizing chemicals induces the production by epidermal cells of a variety of cytokines including interleukins 1 (alpha and beta), 6, 8 and 10 (IL-1alpha, IL-1beta, IL-6, IL-8 and IL-10), granulocyte/macrophage colony-stimulating factor and tumour necrosis factor alpha. There is mounting evidence that keratinocyte-derived cytokines play a role of some importance in cutaneous immune responses and the development of contact sensitization. The induction phase of contact sensitization is dependent upon the action of epidermal Langerhans cells (LC). Following epicutaneous exposure to skin sensitizing chemicals LC are induced to migrate via afferent lymphatics to the draining lymph nodes. During migration, or shortly following arrival in the nodes, LC acquire the characteristics of lymphoid dendritic cells. This functional maturation is accompanied by elevated expression of MHC class II (Ia) antigens and of intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 and Ia facilitates the interaction with, and stimulation of, T lymphocytes by dendritic cells. The role epidermal cytokines play in this process is described. Characterization of the role epidermal cytokines play in regulating LC function may allow not only clarification of the molecular events which initiate skin sensitization, but also provide opportunities to investigate in vitro the consequences of the interaction of chemical allergens with the skin.
Kimber
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Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK.