Modulation of leucocyte adhesion molecules, a T-cell chemotaxin (IL-8) and a regulatory cytokine (TNF-Α) in allergic contact dermatitis (rhus dermatitis)

To understand the molecular events which are important in leucocyte trafficking in cutaneous inflammation, poison ivy/oak extract was applied topically to the skin, and the simultaneous assessment of a variety of clinical and immunopathological parameters performed. The clinical response of subjects was divided into three main groups: I. 2–24 h after application, before the onset of erythema; II, 48 h-1 week after application during maximal clinical changes; III, 2–3 weeks after application when the inflammation had subsided. Six different biopsies per subject were evaluated over the study period and the density of dermal cellular infiltrate, and the distribution of intercellular adhesion molecule-1, (ICAM-1), endothelial leucocyte adhesion molecule-1, (ELAM-1), vascular cell adhesion molecule-1, (VCAM-1), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-Α), determined. Eight hours after exposure, before lymphocytes and monocytes had entered the dermal interstitium or epidermis, the keratinocytes expressed TNF-Α and TCAM-1, whilst the endothelial cells expressed ELAM-1, VCAM-1 and ICAM-1. Group II biopsies revealed increasing keratinocyte expression of TNF-Α and ICAM-1 with the appearance of IL-8, which correlated with the onset of epidermal T-cell trafficking. The endothelium was strongly positive for ELAM-1 and VCAM-1, but there was no influx of neutrophils. Group III biopsies showed a decrease in the expression of ICAM-1, VCAM-1 and FLAM-1 by both keratinocytes and endothelium with a reduction in epidermal/dermal inflammation, although the endothelial cell staining of VCAM-1 and ELAM-1 did not completely disappear. These results suggest that on exposure to poison ivy/oak, keratinocytes rapidly produce TNF-Α which leads to an early autoinduction of ICAM-1, and later IL-8. There is also a paracrine-mediated induction and augmentation of underlying endothelial cell ELAM-1, VCAM-1 and ICAM-1.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71459/1/j.1365-2133.1991.tb04943.x.pd