Cyclosporine A affects the in vitro expression of T cell activation-related molecules and cytokines in dogs

• Published in: Veterinary immunology and immunopathology Vol. 140; no. 3-4; pp. 175 - 180
• Main Authors: Fellman, C.L., Stokes, J.V., Archer, T.M., Pinchuk, L.M., Lunsford, K.V., Mackin, A.J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2011; Amsterdam: Elsevier
• Subjects: Animals; Biomarkers - metabolism; Cyclosporine; Cyclosporine - pharmacology; Cytokine; Cytokines - metabolism; Dog; Dogs - immunology; fas Receptor - metabolism; Flow Cytometry; Immunosuppressive Agents - pharmacology; In Vitro Techniques; Interferon-gamma - metabolism; Interleukin-2; Interleukin-2 - metabolism; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-4 - metabolism; Lymphocyte; Lymphocyte Activation - drug effects; Pharmacodynamics; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Pharmacodynamics; Interleukin-2; Cyclosporine; Dog; Lymphocyte; Cytokine
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2010.11.005

Cyclosporine is a powerful immunosuppressive drug that is being used with increasing frequency to treat a wide range of immune-mediated diseases in the dog. To date, ideal dosing protocols that will achieve immunosuppression with cyclosporine in dogs remain unclear, and standard methods that can measure effectiveness of immunosuppression have not been established. The aim of our study was to evaluate the effects of in vitro cyclosporine exposure on a panel of molecules expressed by activated T cells to ascertain their potential as biomarkers of immunosuppression in dogs. Blood was drawn from six healthy dogs, and peripheral blood mononuclear cells (PBMC) were isolated and activated. Half of the cells were incubated with 200ng/mL cyclosporine prior to activation, and the other half were not exposed to cyclosporine. Samples were analyzed using flow cytometry, and the expression of intracellular cytokines IL-2, IL-4, and IFN-γ was evaluated after 6, 12, and 24h of drug exposure. Each cytokine exhibited a time-dependent suppression profile, and all but two samples activated in the presence of cyclosporine showed lower cytokine expression than untreated controls. We also evaluated the expression of the surface T cell activation molecules CD25 and CD95 by flow cytometry after 36h of drug exposure. Expression of these surface molecules decreased significantly when activated in the presence of cyclosporine. Our results suggest that suppressed expression of the markers related to T cell activation could potentially be utilized as an indicator of the efficacy of cyclosporine therapy in dogs.