Blockade of OX40/OX40 Ligand to Decrease Cytokine messenger RNA Expression in Acute Renal Allograft Rejection In Vitro

Abstract Aim The aim of this study was to investigate cytokine messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) from renal recipients experiencing acute rejection by blocking OX40-OX40L interactions with recombinant human OX40-Fc fusion protein (rhOX40Fc) in vitro. Methods PBMCs were isolated from 20 recipients experiencing acute rejection episodes (rejection group) and 20 recipients with stable graft function (stable group). Levels of Th1 (interferon [IFN]-γ) and Th2 (interleukin [IL]-4) mRNA expressions by PBMCs were measured using real-time reverse transcriptase-polymerase chain reactions. Results IFN-γ mRNA expression levels were significantly higher in the rejection than the stable group ( P < .05). Levels of IL-4 mRNA expression were not significantly different. Among the rejection group, rhOX40Fc reduced significantly the expression of IFN-γ and IL-4 mRNA by anti-CD3-monoclonal antibody stimulated PBMCs ( P < .05, and P < .01, respectively). Conclusions Blocking of the interaction between OX40 and OX40L in vitro inhibited production of Thl and Th2 type cytokines.