An intra-laboratory validation of the Integrated Model for the Differentiation of Skin Reactions (IMDS): discrimination between (photo)allergic and (photo)irritant skin reactions in mice

Abstract

We recently presented a modified local lymph node test which made it possible to quickly and reliably differentiate between irritative and allergic skin reactions with extremely simple parameters. The Integrated Model for the Differentiation of Skin Reactions (IMDS) test combines measurement of cell proliferation in draining lymph nodes with measurement of primary ear swelling after topical application of the test substance on three consecutive days. In contrast to the 'classic' skin sensitisation test in guinea-pigs the IMDS test is considerably faster and is based on objective measured data, not subjective skin evaluations. Like the Local Lymph Node Assay (LLNA), measurement of allergic potential in the IMDS test is based on the underlying immunological mechanisms, but also considers the behaviour of immune competent cells following non-specific activation by irritants. In addition, the IMDS test can employ UV radiation after application of the substance and, therefore, make differentiation possible between different types of skin photoreaction (photoallergy and photoirritation) after both topical and systemic administration. Attempts to achieve this kind of discrimination with the LLNA necessitate considerably greater expenditure, as proliferation in the draining lymph nodes can also be induced by moderate to extreme (photo)irritants. In a previous paper in which we presented the IMDS test, we examined each type of reaction in reference to one single standard; the next logical step was therefore a broad-based intra-laboratory validation. An important factor in the validation was the use of standards that had been thoroughly examined in both guinea pig and mouse systems and were also relevant with regard to estimation of the risk for humans. The data presented here show that the IMDS is a simple and reliable tool for obtaining fast and reproducible assessments of potential (photo)allergic and (photo)irritant skin reactions to substances.

Local lymph node assay with non-radioisotope alternative endpoints.

“…Hariya et al (1999) reported that IL-2 production with lymph node weight and CD4 positive subset ratio in LNC improved sensitivity. Homey et al (1998) and Vohr et al (2000) presented an integrated model for differentiating skin reaction (IMDS), which assesses ear swelling and cell proliferation in lymph nodes.…”

Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: evidence for different activation pattern of immune cells following topical and respiratory induction

“…Modifications of this assay (integrated model for the discrimination of skin reactions; IMDS) verified that methods other than radioactive labelling may be comparably sensitive van Och et al 2000;Vohr et al 2000;Ulrich et al 2001b), and that it is possible to eliminate 'false positive' results induced by irritants. Thus, we asked whether there may be a simplified model analogous to the modified LLNA or IMDS also possible for the respiratory sensitization.…”

“…The underlying mechanisms and the complicated network of cytokine regulation it is now basically understood (Takashima 1995;Homey et al 1997;Leung 1998;Blu¨mel et al 1999). This knowledge about molecular and morphological differentiation during the onset of inflammatory reactions (Avnstrop et al 1989;Ulrich et al 1998;Gerberick et al 1999) led to simplified models for the discrimination between allergic and irritant pathways (Avnstrop et al 1989;Homey et al 1998;Vohr et al 2000). In principle, comparable mechanisms should exist in the mucosa, although carried out by other cell types (epithelial cells, smooth muscle cells, alveolar macrophages, lung fibroblasts etc.).…”

Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy

“…Nevertheless, the fact that the in vivo method cytokine studies used cells that had 'seen' BrdU while those in the ex vivo method never 'saw' the agent (and therefore did not become functionally modified it) might be an additional critical factor that works in the favor of the use of the ex vivo BrdU method to assess 'truer' measures of function of lymphocytes from hosts being used to assess a potential for ACD caused by a test chemical. Homey et al (1998) and Vohr et al (2000) presented an integrated model for differentiating skin (IMDS) reaction that assessed ear swelling and cell proliferation in lymph nodes to detect and differentiate chemical-induced irritant and allergic skin responses. In our study, since DI values were > 1 for all concentrations, DNCB is an allergic compound.…”