Models of Psoriasis and Psoriatic Arthritis
Psoriasis (Ps) is a chronic inflammatory skin disease with systemic manifestations dependent on both genetic and environmental factors. Ps is characterized by a thickening of the epedermis and immune infiltrates throughout the dermis and epidermis, causing skin lesion that affect quality of life. Many patients affected by psoriasis also develop inflammation in other organs, often joints as in psoriatic arthritis (PsA). To study the disease pathogenesis, animal models are a good tool.
The Imiquimod-induced skin inflammation model of Psoriasis (Ps) in mice
The most commonly used model for the disease is the Imiquimod-induced skin inflammation model (IMQ-model). In the IMQ model, Aldara cream (containing 5% IMQ) is applied topically to the ear and shaved back skin on mice daily. IMQ is a potent immune activator and a Toll-like receptor (TLR7/8) agonist that elicits erythema, scaling, keratinocyte proliferation and differentiation as well as dermal T cell infiltrations upon administration. The resulting inflammation shows similarities with the human disease and a cytokine pathway mirroring the one seen in the human Ps, with a dependency of Th17 cells and the IL-23 /IL-17 axis.
Onset of skin inflammation is most often observed a few days after initiation of the application of Aldara cream (5% IMQ). The mice develop an acute inflammation in the skin of the ears and back where the cream has been applied, which is enhanced throughout the experiment (termination day 7). Disease development is also accompanied with increased spleen size. Histology of skin resembles human Ps with infiltrating cells and thickening of the epidermis.
The Mannan induced Psoriatic Arthritis (MiP) model in mice
The mannan (Saccharomyces Cerevisiae) induced PsA model (MiP) in mice is a newly developed model in which both skin lesions resembling those seen in Ps as well as the joint inflammation of PsA can be found. Disease is mediated by TNF-a produced by macrophages which leads to T cell activation and IL-17A production. The increased level of IL-17A recruit neutrophils to joint and skin and results in an inflammatory response. Repeated mannan injections (every 7th day) give rise to a chronic relapsing disease.
Onset of joint and skin inflammation is seen within a few days after the mannan injection and slowly heals out after one week if not reactivated by a second mannan injection. In addition to the clinical evaluation of inflammation, disease progression is also accompanied by increased number of cells in the spleen.
Restimulation assays in the Mannan induced Psoriatic arthritis (MiP) model in mice
The MiP model can also be used for ex vivo stimulation assays, either as a follow up assay at termination of the in vivo experiment or as a stand alone assay for initial investigation of efficacy and dosing. Spleens from animals induced with MiP show a greater number of splenocytes at termination compared to naive spleens or spleens from treated MiP mice. Splenocytes can be cultured in presence of the lectin activator Concanavalin A (ConA) and cellular and cytokine responses can be measured. Splenocytes can either be taken from mice treated in vivo to investigate effect of drug on restimulation, or alternatively, cells from non-treated mice can be used for investigation of effect of test item ex vivo.