Recovery of T‐cell function in healthy dogs following cessation of oral cyclosporine administration

• Published in: Veterinary medicine and science 2020-08, Vol.6 (3), p.277-282
• Main Authors: Narayanan, Lakshmi, Mulligan, Charlee, Durso, Lisa, Thames, Brittany, Thomason, John, Fellman, Claire, Mackin, Andrew, Wills, Robert, Archer, Todd
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; cyclosporine; Cyclosporine - adverse effects; Cyclosporins; Cytokines; Dermatitis; Disease; Dogs; Dogs - immunology; Drug dosages; Female; Fungal infections; Gene expression; Immune system; Immunosuppressive Agents - administration & dosage; Interferon; interferon gamma; Interferon-gamma - immunology; Interferon-gamma - metabolism; interleukin 2; Interleukin-2 - immunology; Interleukin-2 - metabolism; Laboratory animals; Lymphocytes; Original; Reverse Transcriptase Polymerase Chain Reaction; T cell; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thermal cycling; Tumor necrosis factor-TNF; Veterinary medicine
• ISSN: 2053-1095; 2053-1095
• DOI: 10.1002/vms3.230

Cyclosporine is a potent immunosuppressive agent used to treat immune‐mediated disorders in dogs. Secondary infections sometimes necessitate withdrawal of cyclosporine, but it is not known how long it takes for the immune system to recover after cessation of cyclosporine. Our goal was to utilize a validated RT‐qPCR assay in dogs to assess recovery time of the T‐cell cytokines IL‐2 and IFN‐γ after discontinuation of cyclosporine. Six healthy dogs were given oral cyclosporine (10 mg/kg every 12 hr) for 1 week, with samples collected for measurement of cytokine gene expression prior to treatment, and on the last day of therapy. Cyclosporine was then discontinued, and samples were collected daily for an additional 7 days. Results revealed that there was a significant difference in cytokine expression when comparing pre‐treatment and immediate post‐treatment values, corresponding to marked suppression of T‐cell function. There was no significant difference between pre‐treatment values for either cytokine when compared with any day during the recovery period. Cytokine expression, evaluated as a percentage of pre‐treatment baseline samples, demonstrated progressing return of T‐cell function after drug cessation, with full recovery seen in all dogs by Day 4 of the recovery period. Cyclosporine administration in dogs did result in a significant difference in ∆Ct for cytokine expression when comparing pre‐treatment and immediate post‐treatment values, corresponding to marked suppression of T‐cell function. Cytokine expression, evaluated as a percentage of pre‐treatment baseline samples, demonstrated progressing return of T‐cell function after drug cessation, with full recovery by Day 3 of the recovery period.