Cyclosporine and tacrolimus have inhibitory effects on toll-like receptor signaling after liver transplantation

Abstract

Toll-like receptors (TLRs) play a key role in transplantation biology. The effect of immunosuppression on TLR function after liver transplantation is unknown. Peripheral blood mononuclear cells (PBMCs) from 113 post-liver transplant patients and 13 healthy controls were stimulated with TLR-specific ligands [lipopolysaccharide (TLR4), pan-3-cys (P3C) (TLR2), Poly (I:C) (PIC) (TLR3), R848 (TLR7/8), and CpG (TLR9)] for 24 hours. PBMCs from 5 healthy controls were also cultured with therapeutic concentrations of cyclosporine A (CYA) and tacrolimus (TAC). Cytokine production was measured with enzyme-linked immunosorbent assays and flow cytometry. PBMCs from patients on calcineurin inhibitors afte..