Immunomodulatory in vitro effects of oclacitinib on canine T‐cell proliferation and cytokine production. Issue 1 (12th November 2018)

• Record Type: Journal Article
• Authors: Banovic, Frane; Tarigo, Jaime; Gordon, Hannah; Barber, James P.; Gogal, Robert M.
• Is Part Of: Veterinary dermatology. Volume 30:Issue 1(2019)
• Page Start: 17
• Page End: e6
• Publication Date: 2018-11-12
• Subjects: Veterinary dermatology -- Periodicals; Pet medicine -- Periodicals; 636.08965
• DOI: 10.1111/vde.12698
• Languages: English
• ISSNs: 0959-4493

Abstract

Abstract : Background: Oclacitinib is a Janus kinase inhibitor used to control pruritus and skin lesions in canine allergic skin disease; its effect on canine T cells is not well‐characterized. Hypothesis/Objectives: To evaluate the impact of oclacitinib on cultured T cells using peripheral blood mononuclear cells from dogs. Animals: Six bluetick coonhounds. Methods and materials: Lymphocyte‐enriched cells were incubated with or without the T‐cell mitogen concanavalin A (Con A), oclacitinib (0.5, 1 or 10 μM), ciclosporin (200 ng/mL), Con A + oclacitinib 1 μM and Con A + ciclosporin. We assessed both T‐cell proliferation and the secretion of cytokines. Results: Ciclosporin and oclacitinib both inhibited the spontaneous proliferation of T cells; this effect was significant only after incubation with oclacitinib at 10 μM. At this concentration, oclacitinib significantly reduced the spontaneous secretion of clonal activator cytokines [interleukin (IL)‐2, IL‐15], pro‐inflammatory cytokines (interferon‐gamma (IFN‐γ), IL‐18) and the regulatory cytokine IL‐10; tumour necrosis factor alpha (TNF‐α) and IL‐6 cytokine production was mildly inhibited. After Con A stimulation, only T cells co‐treated with ciclosporin achieved a significant proliferation inhibition and reduction of IL‐2, IL‐10, IL‐15, IL‐18, IFN‐γ and TNF‐α. Surprisingly, oclacitinib at 1 μM (337 ng/mL, corresponding to the oral dosage of 0.4–0.6 mg/kg) did not significantly affect Con A‐stimulated T‐cell proliferation nor cytokine production (IL‐2, IL‐10, IL‐15, IL‐18, IFN‐γ and TNF‐α). Conclusions: Although a limited number of dogs were investigated, these preliminary results suggest that oclacitinib appears to have immunosuppressive properties, but only at dosages above those used to treat allergic pruritus in dogs. Abstract : Background – Oclacitinib is a Janus kinase inhibitor used to control pruritus and skin lesions in canine allergic skin disease; its effect on canine T cells is not well‐characterized.Hypothesis/Objectives – To evaluate the impact of oclacitinib on cultured T cells using peripheral blood mononuclear cells from dogs.Conclusions – Although a limited number of dogs were investigated, these preliminary results suggest that oclacitinib appears to have immunosuppressive properties, but only at dosages above those used to treat allergic pruritus in dogs.