Epidermal cytokines and skin sensitization hazard.
The induction phase of skin sensitization is associated with the passage of antigen-bearing Langerhans cells (LC) from the epidermis to the draining lymph nodes. Recent investigations have revealed that the induction of LC migration following topical sensitization is dependent on tumour necrosis factor alpha (TNF-alpha), an epidermal cytokine. While in transit to the lymph nodes LC are subject to both phenotypic and functional maturation which, by analogy with in vitro studies, is also effected by epidermal cytokines (granulocyte/macrophage colony-stimulating factor, GM-CSF and interleukin-1, IL-1). It is now apparent that Langerhans cell function, the induction of cutaneous immune responses and effective sensitization are dependent on the availability of such cytokines and that contact allergens are able to provoke their production by keratinocytes and by Langerhans cells themselves. The development of screening strategies for the evaluation of skin sensitization potential as a function of epidermal cytokine production is discussed.
Cumberbatch
M
M
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK.
Kimber
I
I