Immunomodulatory in vitro effects of oclacitinib on canine T‐cell proliferation and cytokine production
2019
Banovic, Frane | Tarigo, Jaime | Gordon, Hannah | Barber, James | Gogal, Robert M. Jr
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.
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