Skin inflammation models

Contact dermatitis is an inflammatory skin reaction caused when the skin comes into direct contact with an irritant stimulus and is characterised by a rash, itching and redness of the affected area. Clinical diagnosis is usually achieved by physical examination of the affected area. Histological examination of skin samples shows spongiosis, epidermal cell necrosis and neutrophilic infiltration. Contact dermatitis presents an immune mediated reaction known to involve both T helper 1 cell (Th1) and Th2 response. Charles River has established multiple translational animal models of contact dermatitis that can follow an acute or chronic time-course, in addition to other skin inflammation models (e.g. Psoriasis, DTH, Atopic Dermatitis, Scleroderma), including:

  • Allergic Contact Dermatitis

    In the acute model of allergic contact dermatitis, disease state can be achieved by a topical application of an allergen, usually oxazolone or 2,4,6-trinitrochlorobenzene (TNBC). The chosen disease inducing agent is topically applied to the clipped abdomen (sensitisation). Several days (usually 7 days) after sensitisation the same disease inducing agent is applied topically to the ear which will result in an inflammatory response known as challenge. The acute model is characterized by a Th1 response. For chronic models the challenge is repeated for up to 4 weeks and results in a Th2 response. In both models, ear swelling is measured using digital callipers to monitor the inflammatory response.

    Validation Data

    Graph showing ear swelling in 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis model. Graph shows ear swelling data as the difference between the challenged and control ear thickness measurements; the graph shows efficacy of Cyclosporin A (CSA) compared to the vehicle.
    Figure 1: Graph showing ear swelling data as the difference between the challenged and control ear thickness measurements in the 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis model. The graph shows efficacy of Cyclosporin A (CSA) compared to the vehicle.

     

    Graph showing cytokine cytokine levels ear homogenates in oxazolone-induced allergic contact dermatitis model. The data shows reduced levels of IL-1β in the Betamethasone group when compared to the vehicle.
    Figure 2: Graph showing cytokine levels in ear homogenates from the oxazolone allergic contact dermatitis model. The data shows reduced levels of IL-1β in the Betamethasone group when compared to the vehicle.

  • Irritant Contact Dermatitis

    Acute irritant contact dermatitis models are induced by a topical application of an irritant, typically capsaicin or arachidonic acid; other irritants that can be used are methyl salicylate, phenol, croton oil, ethyl phenyl propionate or phorbol 12-myristate-13-acetate. Topical applications are typically performed on one ear (ipsilateral) while the contralateral ear is used as a control. Ear thickness is usually measured 24 hours after application of disease inducing agent. Peak disease corresponding to a moderate erythema and a moderate swelling is observed half an hour to 24 hours after topical application of the sensitizing agent and the symptoms decrease after 24 hours. For the chronic model the disease inducing agent is reapplied for up to 4 weeks.

    Validation Data

    Ear Swelling in Capsaicin induced irritant contact dermatitis model. Graph showing ear swelling presented as the difference between the challenged and control ear thickness measurements in the capsaicin irritant contact dermatitis model. The graph shows efficacy of dexamethasone compared to the vehicle at 24hrs post challenge
    Figure 3: Graph showing ear swelling presented as the difference between the challenged and control ear thickness measurements in the capsaicin irritant contact dermatitis model. The graph shows efficacy of dexamethasone compared to the vehicle at 24hrs post challenge.

     

    Histopathology (H&E staining) image of control untreated skin group, in the Capsaicin induced irritant contact dermatitis model
    Figure 4: Histopathology image (H&E staining) of untreated control skin.

     

    Histopathology of capsaisin induced irritant contact dermatitis model. Histopathology image (H&E staining) of skin post topical application of capsaicin shows epidermal hyperplasia with focal haemorrhages and dermal oedema, as markers of contact dermatitis.
    Figure 5: Histopathology image (H&E staining) of skin post topical application of capsaicin showing epidermal hyperplasia with focal haemorrhages and dermal oedema.

    Model Readouts:

    • PK/PD blood collections
    • Myeloperoxidase activity
    • Histopathological evaluation
    • Ear thickness measurements
    • Cytokine/chemokine analysis of skin biopsies and lymph nodes
Hands rubbing medication on skin inflammation.

In Vivo Dermal Models for Drug Screening

This webinar explains various in vivo dermal models that mimic inflammatory and autoimmune skin diseases. Watch Now


Contact Dermatitis Frequently Asked Questions (FAQs):

  • Which models are best for testing therapeutics against Allergic contact dermatitis?

    Allergic contact dermatitis is characterised by a T cell response in both humans and mice, and therapies targeting this response blocks the associated contact hypersensitivity response. Although other targets can be effective, as disease progresses in 2 distinct phases; sensitisation phase where Langerhans take up haptenated proteins, which are presented to T cells, then in the elicitation phase the body is re-exposed to the same hapten. Allergens such as oxazolone or 2,4,6-trinitrochlorobenzene (TNBC) can fully induce this contact hypersensitivity response, and mimic the histopathology seen in humans.

  • What is the difference between the animal models for allergic and irritant contact dermatitis?

    The Irritant contact dermatitis model is induced via foreign substances that damage the skin (e.g. capsaicin or arachidonic acid), however allergic contact dermatitis models are induced by haptens that cause an immune response known as contact hypersensitivity. Each model is induced in a method consistent with the associated human disease, for optimal clinical relevance.