The protein kinase C inhibitor sotrastaurin allows regulatory T cell function.
de Weerd A, Kho M, et al.Clinical and experimental immunology 2014; 175(2): 296-304
Aims
To compare sotrastaurin and the calcineurin inhibitor neoral in de novo renal transplant recipients. An ex vivo study on patient samples was used to investigate the frequency and function of FoxP3+CD4+CD25high T cells. An in vitro study on samples of blood bank volunteers was conducted to study the different effects of sotrastaurin on T effector and regulatory cells.
Interventions
Patients were administered with sotrastaurin 300mg twice daily or neoral (starting dose 4mg/kg/day aimed trough levels were 100–200 ng/mL (month 1), 75–150 ng/mL (months 2–3), 50–100 ng/mL (months 4–5) and 25–50 ng/mL (months 6–12)).
Participants
21 de novo renal transplant recipients.
Outcomes
The study outcomes included proliferation of peripheral blood mononuclear cells, expression of phosphorylated (p)STAT5, sotrastaurin and the suppressive function of CD4+CD25high T cells in vitro, peripheral lymphocytes and Tregs.
Follow-up
6 months.
CET Conclusions
This manuscript reports a substudy of a small number of participants of a randomised controlled trial of Sotrastaurin (a protein kinase C inhibitor) and cyclosporine Neoral. The authors demonstrate that whilst Sotrastaurin is a potent inhibitor of alloreactive T-cells, it does not affect the function of regulatory T-cells. This is in contrast to the effect of CNIs, which in this and previous work have been demonstrated to inhibit regulatory T-cell function.
Data analysis
Per protocol analysis
Trial registration
Not reported.