IN-VITRO MODEL FOR CONTACT SENSITIZATION .2. INDUCTION OF IL-1-BETA MESSENGER-RNA IN HUMAN BLOOD-DERIVED DENDRITIC CELLS BY CONTACT SENSITIZERS

Epidermal mRNA for interleukin 1 beta (IL-1 beta) has been shown to be increased following exposure of mouse skin to sensitizing compounds. In addition, this early upregulation of IL-1 beta was specific for con tact sensitizers, while expression of IL-1 beta was unaffected by irri tants. Langerhans cells are the major source of IL-1 beta within the e pidermis in the induction phase of skin sensitization. Since the isola tion of Langerhans cells from skin biopsies results only in low freque ncies, we decided to use dendritic cells (DCs) generated from peripher al blood as Langerhans cell equivalents to investigate the ability of five contact sensitizers and one irritant to induce IL-1 beta gene exp ression in vitro. For our studies we cultivated DCs in serum-free medi um supplemented with granulocyte/macrophage-colony stimulation factor (GM-CSF) and interleukin 4 (IL-4). The DCs showed a typical dendritic morphology, a characteristic expression of surface markers and high st imulatory capacity for autologous T cells. 5-day-old DCs were incubate d with subtoxic concentrations of the contact sensitizers pentadecyl-c atechol, 2,4,6-trinitrobenezene sulfonic acid, 2,4-dinitrofluorobenzen e, NiSO4, K2Cr2O7 and the irritant sodium dodecyl sulfate. IL-1 beta m RNA expression was detected by using the reverse transcriptase-polymer ase chain reaction (RT-PCR) technique and non-radioactive hybridizatio n procedures. For all contact sensitizers, expression of IL-1 beta mRN A increased, whereas treatment with the irritant SDS had no significan t effect on IL-1 beta expression. Thus we developed an in vitro system , which may be useful to evaluate allergic potentials of chemicals and products. (C) 1997 Elsevier Science Ltd.