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

Abstract

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 (TGFβ)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.

Non-controlled, open-label trial to assess clinical and immunological parameters in atopic dogs feeding monoprotein grain free diet versus a standard grain diet

“…Instead, Herrmann et al. ( 2023 ) did not find any effect of oclacitinib on the percentage of regulatory T cells (CD4 + CD25 + FoxP3 + ), indicating the variation of results found depending on whether the studies are done with peripheral lymphocytes in vivo or after stimulation with antigens with in vitro studies. This observation did not found in our atopic dogs, and no effect of the oclacitinib treatment on lymphocyte population in vivo was detected, probably because the dose was low.…”

“… 2016 ; Herrmann et al. 2023 ) in atopic dogs, but in the study by Jasiecka-Mikołajczyk et al. ( 2018 ) demonstrated that oclacitinib had no influence on the expression of CD25 and Foxp3 on CD4 + and CD8 + T cells, but a dramatic loss of CD4 + and CD8 + T cells was caused by oclacitinib when the drug was evaluated in vitro .…”

Oclacitinib 10 years later: lessons learned and directions for the future

“…Evaluations of complete blood counts and serum biochemistries for patients on long-term oclacitinib reported mild leukopenia (most commonly neutropenia and rarely lymphopenia). 3,8 Rare reports 10 of changes in the serum biochemistry and urinalysis have been reported but do not often warrant cessation of therapy. In initial studies, 10 symptoms of urinary tract infections were seen in 0.5% to 11.3% of dogs that were on chronic oclacitinib; however, quantitative bacterial cultures were not performed.…”