The effect of Monocarboxylate Transporter (MCT1) inhibitor, AR-C117977 on accelerated rejection of cardiac grafts in pre-sensitised rats and concordant xenotransplantation

Clara Paul,Susan Edwards,Agneta Montgomery,Zhongquan Qi,Elain Holness,Henrik Ekberg,Robert Bundick,David Donald,Robert Craggs,Clare Murray

doi:10.15761/tit.1000241

Abstract

The effect of Monocarboxylate Transporter (MCT1) inhibitor, AR-C117977 on accelerated rejection of cardiac grafts in pre-sensitised rats and concordant xenotransplantation

Highlights

For many years, the importance of antibody formation in chronic rejection and how to prevent chronic rejection has been discussed widely [1,2,3]
Acute rejection was the main problem in transplantation and there were only a few immunosuppressive therapies available
Splenocytes from Balb/c mice were stimulated with LPS or 8MG to induce proliferation and antibody production (Figure 1), AR-C117977 and CsA inhibited proliferation in response to both stimuli (Figure 1A and 1B)

Summary

Introduction

The importance of antibody formation in chronic rejection and how to prevent chronic rejection has been discussed widely [1,2,3]. Acute rejection was the main problem in transplantation and there were only a few immunosuppressive therapies available. The main problem is to detect and prevent chronic rejection. Recipients with donor specific antibodies are in need of high immunosuppressive regimes to prevent graft loss. Combinations of different drugs in moderate doses would theoretically potentiate the immunosuppressive effect by blocking multiple pathways. Most centres worldwide use a cocktail of different drugs at lower doses to minimize side-effects of the immunosuppressive drugs but with sufficient efficacy to prevent acute rejection. There is still no drug on the market efficient enough to solve chronic rejection and formation of antibodies

Objectives

Methods

Results

Conclusion