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Cytokine regulation of chemical sensitization
I Kimber1, M R Holliday, R J Dearman
1Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Abstract:
The skin is an immunologically active tissue. Epidermal cells, both keratinocytes and Langerhans cells (LC), produce constitutively or can be stimulated to produce a variety of cytokines, many of which play important roles in the induction and regulation of allergic responses to sensitizing chemicals. Tumor necrosis factor alpha (TNF-alpha) provides the signal for LC migration from the skin and granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin 1 (IL-1) and other cytokines effect the functional maturation of LC and their acquisition of immunostimulatory potential. The initial stimulus for induced or increased epidermal cytokine production derives from chemical exposure, or some other form of skin trauma. However, some epidermal cytokines are regulated in paracrine or autocrine fashion by other cytokines produced locally. The availability of epidermal cytokines has a major impact on the induction of sensitization and on the characteristics of immune responses to chemical allergens.