The Murine Local Lymph Node Assay

Allergies make up a major global health problem. After dermal contact with allergens, susceptible individuals are prone to allergic contact dermatitis which consists of two stages: skin exposure causing immunological priming and the acquisition of skin sensitization. Up until 2002, the most widely used animal models for the evaluation of the skin sensitizing potential of compounds were guinea pig models containing the induction phase as well as the challenge phase to elicit a sensitization response. In 1986, the murine local lymph node assay (LLNA) was described by Kimber et al. as a method for assessing the contact sensitization potential of compounds. Since that time, the LLNA has undergone extensive evaluation and validation and is the only validated in vivo method for detection of skin sensitization. Focusing on the induction phase only, the murine LLNA does not have a challenge phase. The contact allergenic potential of a compound is evaluated by the cellular proliferation of the draining lymph nodes of mice following topical treatment of the ear flap with test compound. This stimulation reflects the induction of an immune response. The LLNA utilizes three concentrations allowing for the assessment of a dose response relation. In order to distinguish between irritant and allergic responses in the LLNA, several modifications and alternative endpoints for the LLNA have been investigated. Compared to the guinea pig studies, the LLNA reduces the number of animals, provides objective and quantitative endpoints and is less prone to subjective interpretation.

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