Generation of leukotrienes from normal epidermis and their demonstration in cutaneous disease

In order to evaluate the significance of chemotactic leukotrienes in cutaneous disease, synthetic leukotriene B4 and its metabolites were examined during in vitro chemotaxis. Leukotriene B4, and less so 20-OH-leukotriene B4, were chemotactic for neutrophils and eosinophils, with a preferential attraction of eosinophils. The responsiveness of human monocytes towards leukotriene B4 was relatively low. Normal cells and cells from different patients varied in their quantitative response. Cells from patients with eczema and T-cell lymphoma tended to migrate less than those from patients with other inflammatory diseases. Leukotrienes are generated from several types of peripheral leukocytes. In order to examine whether resident cells of the skin can also produce these factors, isolated human and murine epidermal cells were examined for their ability to generate leukotriene B4 and leukotriene C4 in vitro. Arachidonic acid, and less so the ionophore A 23187, induced the generation of both types of factors, based on the finding in the bioassay, reverse-phase high-pressure liquid chromatography and radioimmunoassays. The same factors were demonstrated by either or all of these methods in skin biopsies, scales, blisters or suction blisters of patients with psoriasis, pitysiasis rubra pilaris, dyshidrosis, bullous pemphigoid, pressure urticaria, urticaria pigmentosa and drug reactions, but not in Sézary syndrome nor in callus and skin biopsies of normal controls. These findings underline the fact that the leukotrienes are potent inflammatory mediators in diverse skin diseases, but that they are not limited to any specific disease. Furthermore, a relationship between leukotrienes and tissue eosinophilia does not exist.