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In previous studies, we showed that a number of aspects of the histopathology of irritant contact dermatitis arc profoundly influenced by the chemical nature of the irritant applied. We report here that this phenomenon also extends to the infiltration of leukocytes into the epidermis. Healthy volunteers were patch tested with the following irritants and their appropriate controls: benzalkonium chloride, sodium lauryl sulphate, crown oil, dithranol, nonanoic acid, and propylene glycol. After visually grading the intensity of the resulting inflammation, biopsies were removed and the major phenotypic classes of leukocytes identified immunocytochemically. Dermal and epidermal cell densities were determined, and the expression of several activation/proliferation antigens studied. We found a similar pattern of cellular infiltration in the dermis of all irritant groups; the densities of most of the cell types rising in line with the intensity of inflammation. Within the epidermis, however, there were marked differences in the patterns of cellular infiltration between the irritant groups, leading to poorer correlations between leukocyte density and visual grading. The greatest disparity occurred between croton oil and nonanoic acid biopsies, the former being characterized by the influx of large numbers of leukocytes, the latter showing remarkably little exocytosis. Infiltration of neutrophils occurred to varying degrees with all irritants, but a disproportionately large number were present in sodium lauryl sulphate biopsies. All control groups showed a rise in CD4 + cells, with distilled water also producing increases in CD11c+ cells and neutrophils. A selective influx of CD25 + cells occurred in the epidermis of both irritant and control groups. Our observations further highlight the heterogeneous nature of irritant contact dermatitis, and confirm previous findings that visually negative control patch tests show marked cellular reactivity.

The expression of three immunoregulatory surface antigens by epidermal keratinocytes was studied in irritant contact dermatitis (ICD), in order to assess whether keratinocytes have a modulatory role in the pathogenesis of this disorder. Biopsies were taken from 48-h patch test reactions to six structurally unrelated irritants, and frozen sections immunolabeled with monoclonal antibodies to the major histocompatibility complex class II antigen, HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and the 88-Kd glycoprotein CD36 (OKM5), as well as to the CD3 (T cells) and CD11a (lymphocyte function associated antigen-1, LFA-1) antigens. We found that there was very limited expression of HLA-DR by keratinocytes, with no correlation between the extent of HLA-DR positivity and the degree of T cell infiltration into the epidermis and dermis, suggesting that interferon gamma may not be a significant mediator of ICD at 48 h. In contrast, keratinocytes showed extensive upregulation of ICAM-1, with an excellent spatial association between ICAM-1 expression and LFA-1 positive leucocytes in the epidermis. This indicates that keratinocyte ICAM-1 induction is not restricted to diseases in which antigen presentation is pivotal, but that it has a generalized role in cutaneous inflammatory reactions, promoting the infiltration of leucocytes into the epidermis. Immunolabeling with OKM5 revealed that CD36 is present to a variable degree on keratinocytes in normal skin. Differential changes in the pattern of keratinocyte expression occurred between irritants, in a manner that suggested that the CD36 antigen does not act as an adhesion molecule in ICD, but rather that its expression is related to the proliferative state of the epidermis. The results of this study demonstrate that immune-associated antigens are selectively expressed on the surface of keratinocytes in 48-h ICD biopsies, implying that these cells play an important regulatory role in the development of the inflammatory response to irritant chemicals.

In order to gain a greater insight into the complex mechanisms of action of different irritant chemicals on the skin, we have studied the behavior of epidermal CD1+ cells in experimentally induced irritant contact dermatitis. Healthy, human volunteers were patch tested for 48 h with the following six chemically unrelated irritants and their appropriate vehicle controls; benzalkonium chloride, sodium lauryl sulphate, dithranol, nonanoic acid, croton oil, and propylene glycol. After visually assessing and grading the resulting inflammatory reactions, punch biopsies were taken and the morphology and density of CD1+ cells in the epidermis studied using immunocytochemical techniques in combination with image analysis and electron microscopy. Statistically significant decreases in the epidermal density of CD1+ cells occurred in the responses to dithranol (p less than 0.05) and nonanoic acid (p less than 0.01). Importantly, these changes in density were not simply due to variations in the intensity of inflammatory response (r = 0.1157). Alterations in the length of the dendritic processes of CD1+ cells were also induced, and semi-quantitative analysis revealed significant decreases in dendrite length in the reactions to sodium lauryl sulphate (p less than 0.05), nonanoic acid (p less than 0.001), croton oil (p less than 0.05), and dithranol (p less than 0.005). Unlike epidermal density, however, this effect on cell morphology was directly related to the severity of inflammation (r = -0.74, p less than 0.01). Morphologic evidence of cellular injury to Langerhans cells was seen by electron microscopy in the majority of biopsies, although relatively few cells were affected in sodium lauryl sulphate and propylene glycol reactions. Benzalkonium chloride, unlike the other irritants, also induced a state of metabolic activation in a high proportion of epidermal Langerhans cells. Lymphocyte/Langerhans cell apposition was observed in most samples, but was particularly prevalent in the reactions to dithranol. The results of this study demonstrate that significant changes in the morphology and density of Langerhans cells occur in irritant contact dermatitis, some of which are directly influenced by the chemical nature of the irritant.