The induction phase of skin sensitization is associated with the passa
ge of antigen-bearing Langerhans cells (LC) from the epidermis to the
draining lymph nodes. Recent investigations have revealed that the ind
uction of LC migration following topical sensitization is dependent on
tumour necrosis factor alpha (TNF-alpha), an epidermal cytokine. Whil
e 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-stimul
ating 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 produc
tion by keratinocytes and by Langerhans cells themselves. The developm
ent of screening strategies for the evaluation of skin sensitization p
otential as a function of epidermal cytokine production is discussed.