Contact sensitisation and allergic contact dermatitis: Immunobiological mechanisms
Toxicology Letters, 162, (1), . (doi:10.1016/j.toxlet.2005.10.008).
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The dose–response relationships of the human immune system can be defined using the induction and elicitation of lymphocyte mediated allergic reactions to experimental contact sensitisers such as dinitrochlorobenzene (DNCB). Five groups of healthy volunteers received a sensitising dose of DNCB applied to a 3 cm diameter circle on the volar forearm. Doses applied were 62.5 ?g, 125 ?g, 250 ?g, 500 ?g and 1000 ?g. Four weeks later a concentration series of 3.125 ?g, 6.25 ?g, 12.5 ?g and 25 ?g was applied to the upper inner arm on 1 cm paper discs which were removed after 6 h. Forty-eight hours later the responses were scored clinically and thickness measured with callipers. The proportion of people reacting to the challenge doses showed a sigmoid log-dose–response curve, 100% reacting to 500 ?g. The responses to challenge also showed a log-dose–reponse. As sensitising dose increased so more people were sensitised to a proportionately greater degree. These dose–response relationships reflect the effects of increasing the concentration of sensitiser on a fixed area. The effect was examined of keeping the concentration per sq cm constant but of varying the total area. When 35.4 ?g/cm2, which sensitised 80% of people when applied to a circle 3 cm diameter (area 7.1 cm2), was applied on a 1.5 cm diameter circle or 4.5 cm diameter, there were no differences in the proportions sensitised or their degree of reactivity. This was clearly on the plateau for the sensitising effect. However, when the same concentration per cm2 was applied on a 3 mm diameter area much weaker sensitisation was obtained. This shows the concentration of sensitiser per unit area is the critical determinant of whether sensitisation occurs, whereas the total dose may be varied over a wide range, but if the concentration per unit area is constant there is no effect on sensitising potency. In other words few Langerhans cells presenting many antigen molecules per cell is a much more potent sensitising stimulus than the same number of molecules presented by many Langerhans cells, each presenting few molecules. These observations clearly have important implications across the whole field of risk assessment for induction of contact sensitivity.
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