IL‐31‐induced pruritus in dogs: a novel experimental model to evaluate anti‐pruritic effects of canine therapeutics

Abstract

BackgroundPruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL‐31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs.Hypothesis/ObjectivesThe objectives were to characterize an IL‐31‐induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti‐pruritic effects of oclacitinib against those of prednisolone and dexamethasone.AnimalsPurpose‐bred beagle dogs were used in all studies.MethodsRandomized, blinded, placebo‐controlled studies were designed to evaluate and compare the anti‐pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL‐31. Video surveillance was used to monitor and score pruritic behaviours in study animals.ResultsPrednisolone [0.5 mg/kg, per os (p.o.)] reduced IL‐31‐induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL‐31‐induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti‐pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed.Conclusion and clinical importanceThe efficacy of prednisolone, dexamethasone and oclacitinib in the IL‐31‐induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations.

Canine models of allergic skin disease

“…Should we take it that chloroquine is a mediator of canine AD? In a study published in Veterinary Dermatology , similar conclusions were made about the injection of IL‐31 . The understanding in this and another study from the same group, was that if we inject IL‐31 and induce pruritus, it means that IL‐31 is an important mediator of allergic skin diseases such as AD and that this model can be used to test new therapeutics.…”

Investigation of the correlation of serum IL‐31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs

“…The correlation between clinical scores and IL‐31 after allergen exposure is of significance. Currently, IL‐31 has been shown to induce pruritus in dogs, yet its role in canine AD (cAD) still needs elucidation. One initial study importantly failed to detect IL‐31 mRNA in the skin of atopic dogs although it was able to report it in other tissues .…”

Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca

“…The advantage of topical administration of JAK inhibitors is that they are small molecules that easily penetrate skin barriers and are well tolerated by human patients . In mice, topical administration resulted in a reduction in the skin swelling that was not seen in animals treated orally, with a reduction in epidermal hyperplasia, parakeratosis, dermal edema, and inflammatory cells infiltration . In dogs topical oclacitinib and tofatinib reduce dermal cellular infiltrates, especially eosinophils and mast cells .…”

“…Oclacitinib is the first JAK inhibitor developed and commercially approved for use in dogs and it is selective for the JAK1 enzyme . JAK‐dependent cytokines and some growth factors utilize the JAK pathway to activate DNA transcription, resulting in transduction of interleukins that evoke and maintain inflammation and pruritus in allergic diseases and stimulate T‐cell proliferation …”