leukotriene-b4 and Dermatitis--Irritant

We assessed the effects of physical and chemical irritants on a profile of acute inflammatory mediators in normal human skin. Skin damage in both cases is accompanied by a flux of inflammatory processes and repair mechanisms, which remain imprecisely understood. We used 10 sequential cellotape strips or topical application of 0.075% capsaicin as skin irritants and characterized the subsequent production and/or release of inflammatory mediators in suction blister fluids from human skin in vivo. In tape stripped skin, levels of prostaglandin E2 and interleukin-1alpha were increased 3.4-fold and 3.3-fold, respectively (p<0.0001; p<0.02), levels of tumour necrosis factor-alpha were decreased 3.0-fold (p<0.01), whereas levels of interleukin-6 and leukotriene B4 in blister fluids remained relatively unchanged. For the capsaicin-treated skin, levels of mediators showed only minor differences when compared with matched controls. However, a correlation was observed between levels of prostaglandin E2 and interleukin-1alpha in capsaicin pre-treated blister fluids (r=0.58, p<0.01, n=19). These data are consistent with prostaglandin E2 and interleukin-1alpha playing key roles in acute skin responses to mild irritants.

Topics: Acute Disease; Adhesives; Capsaicin; Cytokines; Dermatitis, Irritant; Dinoprostone; Eicosanoids; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Leukotriene B4; Skin; Tumor Necrosis Factor-alpha

Development, peak and healing lesions were induced in the skin of rabbits by topical applications (on different days) of the chemical irritant sulfur mustard (SM). Immediately after the rabbits were euthanized, the intact lesions were excised and organ-cultured for 17 to 20 hours. The culture fluids from early, peak and healing SM lesions all showed high chemotactic activity for both PMN and MN. This finding suggests that the PMN and MN, seen microscopically in tissue sections of the lesions, were entering continuously, even during the healing process. The chemotaxins identified were the eicosanoid LTB4, the chemokine IL-8, and proteases producing the complement fragment C5a. Other studies from our laboratory showed that the number of cells containing IL-1, IL-8, MCP-1, and GRO mRNAs was increased in SM lesions. Chemotactic activity was released by both live and dead (frozen and thawed) cell suspensions of PMN, MN, and fibroblasts, suggesting that these cells were major sources of the chemotaxins produced by the SM lesion explants. Explants of normal skin produced considerable chemotactic activity for MN, but not for PMN. Chemotactic activity for PMN, and the release of LTB4, IL-8 and proteases cleaving C5 to C5a, occurred only in explants infiltrated by leukocytes.

Topics: Animals; Chemotactic Factors; Complement Activation; Dermatitis, Irritant; Inflammation Mediators; Interleukin-8; Irritants; Leukocytes, Mononuclear; Leukotriene B4; Macrophages; Mustard Gas; Neutrophils; Organ Culture Techniques; Rabbits; Skin

Application of leukotriene B4 (LTB4) to normal human skin induces changes similar to those found in psoriatic skin, and it has proved to be a useful model for studying the pathogenesis and treatment of psoriasis. We studied the expression patterns of molecules that have recently been shown to be altered in lesional psoriatic skin, including the extracellular matrix protein tenascin (TN) and the basement membrane and cell surface-associated heparan sulfate proteoglycans (HSPGs). During 72-h the expression of these markers was studied immunohistochemically and the expression of TN was correlated with epidermal proliferation and influx of inflammatory cells. Following the peak influx of polymorphonuclear leukocytes, a marked increase in TN expression was noted in the papillary dermis 72 h after LTB4 application. The expression patterns of basal membrane-associated epitopes of HSPG remained unaltered, whereas the expression of cell surface-associated HSPG disappeared 72 h after LTB4 application. A significant correlation was found between dermal TN expression and epidermal hyperproliferation, and between TN expression and the presence of dermal T cells. These findings indicate that the model of LTB4-induced acute cutaneous inflammation displays many characteristics of early psoriatic lesions and could serve as a model to study some of the cell biological changes in this disease.

Topics: Administration, Cutaneous; Adult; Cell Division; Dermatitis, Irritant; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Immunohistochemistry; Inflammation; Leukotriene B4; Male; Models, Biological; Proteoglycans; Psoriasis; Skin; Tenascin