Studies on the cellular interactions involved in experimental and chronic irritant dermatitis

Abstract

Chronic irritant contact dermatitis (ICD) is a common clinical problem, arising from contact with a diverse range of irritants, affecting people both in the workplace and the home. Previous studies have concentrated on the late acute irritant response (24 hours onwards) in normal volunteers. To date there is limited knowledge of acute irritant reactions in patients with established ICD. For this reason we have compared the effect of three chemically diverse common irritants on 100 patients with a history of chronic ICD for more than 6 weeks, and 31 normal volunteers. The irritants were titrated on normal skin to induce similar grades of erythema by 48 hours. The final concentrations, 80% nonanoic acid (NA), 5% sodium Iaury! sulphate (SLS) and 0.01% dithranol (DL) were applied to the volar aspect of the forearm for various timepoints up to 48 hours. Samples were obtained from punch biopsies and suction blisters enabling us to study the cellular and molecular mechanisms associated with the onset of irritant reactions. In addition this has allowed comparisons to be made between acute reactions in ICD patients with previous data from normal volunteers. Immunohistochemical methods were used to investigate a number of parameters, the findings of which were entered onto a database and statistically analysed. DL irritation evoked minimal histopathological changes. Epidermal damage however, was observed after both NA and SLS application. NA irritation profoundly affected the epidermal LC population, inducing redistribution, apoptosis and a dramatic decrease in LC numbers by 24 hours. Keratinocyte (KC) apoptosis and mild spongiosis was also evident. In contrast SLS irritation had a marked affect upon the epidermal KC population, inducing proliferation, parakeratosis, severe oedema and focal KC activation by 24 and 48 hours. KC activation, defined by .tvrn:C IT and CD54 expression accompanied an extensive leucocyte exocytosis. SLS irritation also reduced epidermal LC numbers by 48 hours, but not as a result of apoptosis. These findings suggest that for the two irritants different mechanisms are involved in LC reduction and therefore have important implications for antigen presentation and immune responses. KC activation and the resultant leucocyte influx were probably triggered through cytokine production. We suggest that the potent T cell and neutrophil chemoattractant IL-8, present after SLS application, was responsible for the heavy dermal and subsequent epidermal leucocyte influx observed by 24 and 48 hours. In the case of NA irritation leucocyte infiltration was less significant, neutrophils were present in the papillary dermis infiltrate at 6 hours, although this influx was not sustained. In contrast, SLS irritation caused dermal accumulation of larger numbers of neutrophils at 24 and 48 hours. Western blotting studies revealed no evidence for the involvement of autoimmune mechanisms in the pathogenesis of either irritant reaction. Our results clearly indicate that the pathological processes induced by NA or SLS are distinct despite comparable clinical reactions. Both irritants provoked epidermal damage, differentially affecting the epidermal architecture and cellular components, with important implications for immune responses.