Effects of cyclosporine on feline lymphocytes activated in vitro

Abstract

Cyclosporine A (CsA) is a calcineurin inhibitor that is known to decrease lymphocyte expression of NFAT-regulated cytokines in humans, dogs and cats, and thereby depress lymphocyte function. Less is known about the effects of CsA on lymphocytes in cats than in other species. Peripheral blood mononuclear cells (PBMCs) were isolated from 6 healthy cats. PBMCs were exposed to i) no treatment, ii) 5 μg/ml concavalin A (ConA), iii) 500 ng/ml CsA and iv) 5 μg/ml ConA and 500 ng/ml CsA. The effects of CsA on cell proliferation were assessed via live and necrotic cell counts from day 1 to day 6. Additionally, flow cytometry was utilized to determine the effect of CsA on apoptosis in feline lymphocytes at day 1 and day 5. ConA exposure resulted in increases in cell counts from day 1 to 6, peaking at day 5. CsA inhibited cell proliferation, indicated via decreased live lymphocyte cell counts in the cell cultures exposed to ConA and CsA, compared to the cell cultures exposed to ConA only. Furthermore, CsA induced early and late apoptotic changes in feline PBMCs. Differences in these responses may influence an individual cat's response to cyclosporine therapy.