Evaluation of IL-2 Suppression and Cyclosporine Concentrations in Dogs with Immune-mediated Chronic Hepatitis

Abstract:

Background: Measurement of IL-2 suppression and cyclosporine concentrations are methods to monitor efficacy of cyclosporine therapy in dogs.

Objectives: Determine magnitude of IL-2 suppression and cyclosporine concentrations in dogs receiving modified cyclosporine for treatment of immune-mediated chronic hepatitis (ICH). Determine if cyclosporine achieves target IL-2 suppression, cyclosporine concentrations, and biochemical and histopathologic remission of ICH.Animals: Nineteen client-owned dogs with ICH.

Methods: Dogs were treated with cyclosporine (starting dose of 5mg/kg PO q12) and monitored with serial biochemistry panels, IL-2 suppression, and cyclosporine concentrations at 1, 3, and 6 months. Activated T-cell expression of IL-2 was measured via quantitative reverse transcriptase PCR. Blood trough and peak cyclosporine concentrations were measured, and target concentrations were 600 and 1400 ng/mL, respectively. Liver histopathology was re-evaluated at 6 months. Biochemical and histopathologic remission were defined by ALT

Results: All dogs had moderate/high IL-2 suppression on at least 1 timepoint. By 6 months, mean cyclosporine dose was 7.7 mg/kg/day (range, 2-12.5). However, 12/13 dogs showed moderate/high IL-suppression (mean 70.8%, range 28-88) of which 3/12 and 10/12 were in biochemical and histopathologic remission, respectively. 12/15 dogs met target trough and peak concentrations and only 2/12 dogs were not in histopathologic remission. Despite suboptimal trough concentrations in 4/16 dogs, all 4 had attained histopathologic remission.Conclusions and Clinical Importance: Cyclosporine resulted in moderate/high IL-2 suppression, target peak and trough concentrations, and histopathologic remission in the majority of dogs evaluated.