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Contact sensitisation and allergic contact dermatitis: Immunobiological mechanisms

Contact sensitisation and allergic contact dermatitis: Immunobiological mechanisms
Contact sensitisation and allergic contact dermatitis: Immunobiological mechanisms
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 µg, 125 µg, 250 µg, 500 µg and 1000 µg. Four weeks later a concentration series of 3.125 µg, 6.25 µg, 12.5 µg and 25 µg 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 µg. The responses to challenge also showed a log-dose–response. 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 µg/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.
contact sensitisation, dermatitis, immune response, dose–response
0378-4274
49-54
Friedmann, P.S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Friedmann, P.S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88

Friedmann, P.S. (2006) Contact sensitisation and allergic contact dermatitis: Immunobiological mechanisms. Toxicology Letters, 162 (1), 49-54. (doi:10.1016/j.toxlet.2005.10.008).

Record type: Article

Abstract

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 µg, 125 µg, 250 µg, 500 µg and 1000 µg. Four weeks later a concentration series of 3.125 µg, 6.25 µg, 12.5 µg and 25 µg 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 µg. The responses to challenge also showed a log-dose–response. 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 µg/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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More information

Published date: 2006
Keywords: contact sensitisation, dermatitis, immune response, dose–response

Identifiers

Local EPrints ID: 27063
URI: http://eprints.soton.ac.uk/id/eprint/27063
ISSN: 0378-4274
PURE UUID: 5dbfd1af-e26d-4409-813a-d2ab48aa8808

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Date deposited: 26 Apr 2006
Last modified: 15 Mar 2024 07:15

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Author: P.S. Friedmann

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