DIFFERENTIAL INDUCTION OF INTERCELLULAR-ADHESION MOLECULE-1 IN HUMAN SKIN BY RECOMBINANT CYTOKINES

We examine the effects of the recombinant epidermal cytokines interleukin 1alpha (IL-1alpha), interleukin 1beta (IL-1beta), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), tumor necrosis factor alpha (TNF), and the effect of the lymphokine gamma interferon (gamma-IFN) on the expression of ICAM-1 in short term organ cultures of newborn human foreskins. In normal skin, ICAM-1 was detected immunohistochemically exclusively on endothelial cells. In addition to enhanced ICAM-1 expression by endothelial cells (at 1 h) and keratinocytes (by 6 h) exposed to gamma-IFN, increased endothelial cell expression also resulted at 24 h after exposure to IL-6 and GM-CSF and at 48 h to M-CSF. Dermal dendritic cell reactivity for ICAM-1 was observed at 24 h after supplementation with IL-1alpha, IL-1beta and IL-6, and at 48 h with GM-CSF and M-CSF. Incubation with culture medium alone or with IL-3 resulted in no change in baseline ICAM-I expression on any cell type, and incubation with TNF resulted in enhanced ICAM-1 expression only by endothelial cells. Thus, in skin explants (as opposed to isolated cell in culture), ICAM-1 is induced on various cell types by a wide range of epidermal cytokines, including IL-6, GM-CSF, M-CSF, IL-1alpha and IL-1beta. Endogenous production and release of these cytokines which may stimulate adhesion molecule expression directly or indirectly may govern lymphoid adhesion to specific dermal as well as epidermal types of skin cells under physiologic and pathologic conditions.