Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products.

Abstract

Peritoneal dialysis (PD) is a well-established therapy for end-stage renal failure, but its efficiency is limited by recurrent peritonitis. As PD solutions impair local inflammatory responses within the peritoneal cavity, we have analyzed their influence on the in vitro maturation of human monocyte-derived dendritic cells (MDDC). Evaluation of MDDC maturation parameters [expression of adhesion and costimulatory molecules, receptor-mediated endocytosis, allogeneic T cell activation, production of tumor necrosis factor alpha, interleukin (IL)-6 and IL-12 p70, and nuclear factor (NF)-kappaB activation] revealed that currently used PD solutions differentially inhibit the lipopolysaccharide (LPS)-induced maturation of MDDC, an inhibition that correlated with their ability to impair the LPS-stimulated NF-kappaB activation. Evaluation of PD components revealed that sodium lactate and glucose-degradation products impaired the acquisition of maturation parameters and NF-kappaB activation in a dose-dependent manner. Moreover, PD solutions impaired monocyte-MDDC differentiation, inhibiting the acquisition of DC markers such as CD1a and DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (CD209). These findings have important implications for the initiation of immune responses under high lactate conditions, such as those occurring within tumor tissues or after macrophage activation.