Análise de biomarcadores na dermatite atópica em cães antes e durante o tratamento com maleato de oclacitinib

Abstract

Canine atopic dermatitis is a chronic, pruritic, genetic and inflammatory disease. There are several therapies used to reduce inflammation and provide quality of life for dogs. However, these are life-long therapies. Therefore is essencial to looking for effective effective therapies with reduced long-term side effects. This study consisted of two experiments using 13 dogs with atopic dermatitis. In the first, the objective was to characterize the ex vivo and in vitro immunophenotyping of these dogs by flow cytometry, comparing them with seven healthy dogs. It was observed that atopic dogs had significantly higher values of CD4 + (p = 0.002) and lower values of CD8 + (p = 0.002) and CD14 (p = 0.009), resulting in significantly higher values of CD4+ / CD8+ ratio (p = 0.000). In addition, after dosing intracytoplasmic cytokines (IL-4 and IFN-) on CD4 + and CD8 + lymphocytes in a four-hour culture, significantly higher values were observed in dogs with canine atopic dermatitis. The influence of the antigen Dermatophagoides farinae added to culture was observed only on the increase of the IFN- produced by CD4+. These data indicate that the immunopathogenesis of atopic dermatitis involves a Th1/Th2 response. In the second experiment, we aim to evaluate the efficacy and toxic effects of prolonged use of oclacitinib maleate in the control of canine atopic dermatitis. Oclacitinib maleate was able to significantly reduce pruritus (p = 0.05), as early as the first 14 days (61% reduction and skin lesions (p = 0.000), indicating rapid and prolonged efficacy. The mean values of blood profile remained within the reference standards to dog. Flow cytometric cell analysis indicated a significant increase of CD4 + (p = 0.002) and CD14 (p = 0.001) and a reasonably constant behavior of the CD4+ / CD8+ ratio during the course of treatment. These unpublished results are an indication that oclacitinib maleate at recommended dose does not cause long-term immunosuppression and therefore can be used safely in the long-term control of canine atopicdermatitis. There was no significant effect of oclacitinib maleate on the cytokines IL-4 and IFN- produced by CD4 + and CD8 +, measured after cell culture. This unpublished study corroborates that the main action of the drug is in inhibition of cytokine signaling and not in its production.