Ex vivo effects of oclacitinib and cyclosporin A on canine immune response to Leishmania infantum.

Abstract

Canine leishmaniosis (CanL), caused by Leishmania infantum, is primarily controlled by a Th1-type immune response. Cyclosporin A (CsA) and oclacitinib (Oc) are commonly used immunomodulatory drugs which might affect the immune response of dogs making them more susceptible to developing clinical leishmaniosis. This study aimed to evaluate, ex vivo, the effects of CsA and Oc on the production of IFN-γ, IL-17a, and IL-2 measured by ELISA in response to L. infantum soluble antigen (LSA). Dogs were divided into three groups: healthy seronegative non-IFN-γ producers (group 1, n = 11), healthy seronegative/seropositive IFN-γ producers (group 2, n = 9), and clinically affected seropositive IFN-γ producers (group 3, n = 10). Whole blood assays were stimulated with LSA, Concanavalin A (ConA), or culture medium, in the presence or absence of CsA (200 ng/mL) or Oc (168.5 and 337 ng/mL). CsA significantly reduced the production of all three cytokines in response to both LSA and ConA in groups 2 and 3, and after ConA stimulation in all groups. Oc at 337 ng/mL significantly decreased IFN-γ production only in group 3 after LSA stimulation. In conclusion, CsA broadly suppresses proinflammatory cytokine responses to L. infantum, while Oc shows a more limited effect, reducing IFN-γ only in clinically affected dogs.