Long‐term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T‐cells, IL‐10 and TGF‐β, in dogs with atopic dermatitis

• Published in: Veterinary dermatology 2023-04, Vol.34 (2), p.107-114
• Main Authors: Herrmann, Ina, Mamo, Lisa B., Holmes, Jenny, Mohammed, Javid P., Murphy, K. Marcia, Bizikova, Petra
• Format: Article
• Language: English
• Subjects: Allergens; Animals; Atopic dermatitis; CD25 antigen; CD4 antigen; Cyclosporine - therapeutic use; Cytokines; Dermatitis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - veterinary; Dog Diseases - drug therapy; Dogs; Drug tolerance; Flow cytometry; Foxp3 protein; Growth factors; Immune Tolerance; Immunological tolerance; Immunotherapy; Interleukin-10; Lymphocytes T; Peripheral blood; T-Lymphocytes, Regulatory; Transforming Growth Factor beta - therapeutic use; Transforming Growth Factor beta1 - therapeutic use
• ISSN: 0959-4493; 1365-3164
• DOI: 10.1111/vde.13140

Background Atopic dogs often are managed with allergen‐specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T‐cell (Treg) induction. Hypothesis/Objectives We evaluated Treg cell numbers and serum interleukin (IL)‐10 and transforming growth factor‐beta (TGF‐β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months. Animals We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate‐to‐severe AD and 15 atopic dogs controlled with AIT. Materials and Methods Peripheral blood CD4+CD25+FOXP3+ T‐cell percentages were determined using flow cytometry. Serum concentrations of IL‐10 and TGF‐β1 were measured by enzyme‐linked immunosorbent assay. Results The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT‐treated dogs. No significant differences were detected in IL‐10 and TGF‐β1 serum concentrations between the five groups. Conclusions and Clinical Relevance Lower Treg cell percentages in the CSA‐treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance. Résumé Contexte Les chiens atopiques sont souvent traités avec une immunothérapie spécifique d'allergène (AIT) et des doses concomitantes de ciclosporine ou d'oclacitinib pour atténuer leurs signes cliniques. Les deux médicaments pourraient affecter l'induction de la tolérance appropriée en inhibant l'induction des lymphocytes T régulateurs (Treg). Hypothèse/Objectifs Nous avons évalué le nombre de cellules Treg et les taux sériques d'interleukine (IL)‐10 et de TGF‐β‐1 chez des chiens diagnostiqués avec une dermatite atopique (DA) et traités avec succès par la ciclosporine ou l'oclacitinib pendant neuf mois ou plus. Animaux Nous avons inclus 15 chie