Imiquimod-Induced Psoriasis Model
IMQ-induced Psoriasis Mouse Model / Overview
Introduction
Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis.
IMQ is a Toll-like Receptor (TLR7) agonist that can be applied to mouse skin to elicit erythema, scaling, epidermis hyperplasia, hyperkeratosis, parakeratosis and dermis inflammation. IMQ induces also IL-17/ IL-23 axis cytokines.
Imiquimod-Induced Psoriasis Mouse Model is a convenient, easy-to-use and affordable mouse model of acute inflammatory response, which is widely used in mechanistic pharmacology of pathology and as a pre-clinical animal model for drug screening and testing before clinical testing on volunteers psoriatic patients.
Protocol Summary
- Immunocompetent strains topically applied with IMQ for 5 days
- Evaluation of in vivo parameters:
- Bodyweights / Ear- back tickness
- Macroscopic scoring (erythema / scaling / etc…)
- Epidermis thickness using OCT
- Evaluation of ex vivo parameters:
- Cytokines analysis / Cytometry
- Histology / Anatomo-pathological evaluation
Typical Results
| Evaluation | Parameter | Control group (excipient) | Reference drug (corticoid or immunosuppressor) |
|---|---|---|---|
| In vivo | Bodyweight | Loss on 72h (hydration necessary) | Loss on 72h (hydration necessary) |
| Ear thickness (calipering) | Increase >50% | Increase 20-30% | |
| Back skin scaling (visual/macroscopical scoring) | Scaling moderate to important | Slight scaling | |
| Back skin erythema (visual/macroscopical scoring) | Erythema moderate to important | Slight erythema | |
| Back skin thickness (calipering) | Increase up to 50-100% | Increase 20-30% | |
| Ex vivo (histology) | HES (Comparison Ear) |  |  |
| Epidermis thickness | Important increase vs. sham | Decrease vs. excipient | |
| Dermis thickness | Important increase vs. sham | Decrease vs. excipient | |
| Dermis infiltration | Important increase vs. sham | Decrease vs. excipient | |
| Other observations | Hyperkeratosis with parakeratosis Presence of microabscesses (Munro’s microabscesses) | Parakeratosis absent or slight Munro’s microabscesses absent |
IMQ-induced Psoriasis Mouse Model / Protocol
- Immunomodulator induction / imiquimod topical application
- Immunocompetent rodent sp. (i.e. Balb/c & C57Bl6)
- Environment status is important (SPF vs. non SPF conventional housing)
- Evaluation of:
- Skin thickness measurement (ear / back)
- Erythema / Scaling (Clinical endpoints) / Total scoring
- Blood samplings for circulating and skin biomarkers analysis (cytokines)
- In vivo imaging (OCT)
- Ex vivo imaging (histology HES / IHC : IF)
IMQ-induced Psoriasis Mouse Model / Results
- Sham vs. IMQ-induction typical results:
- Increase of ear & back thickness
- Epidermis thickness / Dermis inflammation increase
- IMQ-induction vs. reference drug typical results:
- Reference drugs: corticoid (topical or oral) / immunosupressors (oral) / TNF inhibitors
- Reduction of ear & back thickness
- Epidermis thickness / Dermis inflammation decrease
IMQ-induced Psoriasis Mouse Model / Conclusion
Imiquimod-Induced Psoriasis Mouse Model is a first intention model, fast and reproducible used a routine model at Imavita.
8 subjects per group are generally sufficient to underline anti-psoriasis effect of new therapeutics (based on difference of at least 20 to 30% of ear / back thickness / epidermis thickness).
Cautions to be taken on this model:
- Housing conditions are important (SPF vs. conventional). Imavita perform this experiment in conventional conditions where results are more reproducible.
- Use of previously untested excipients should be avoided via topical route as they could cause false positive, false negative or local irritation.
- Formulation physico-chemistry must be well known (pH, osmolarity, etc…) as impact on results can be important.
- Drug pharmacokinetics / ADME / transcutaneous passage should be known to optimize dosing.
IMQ-induced Psoriasis Mouse Model / Bibliography
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