P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines.

Abstract

Infectious diseases are among the most morbid events in uremia. The uremic toxin p-cresol may play a role in the immunodeficiency of uremia by depressing phagocyte functional capacity. Leukocyte adhesion to endothelium, a key event in the immune response, is mediated by endothelial adhesion molecules. These include intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, which are induced by various inflammatory cytokines. We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion. Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta). Thereafter, the endothelial molecules ICAM-1, VCAM-1, and E-selectin were quantitated and the monocyte (THP-1) adhesion to HUVEC measured. P-cresol decreased cytokine-induced protein and mRNA expression of ICAM-1 and VCAM-1. In addition, p-cresol significantly decreased the adhesion of THP-1 to cytokine-stimulated HUVEC. P-cresol may play a role in the immune defect of uremic patients by inhibiting cytokine-induced endothelial adhesion molecule expression and endothelium/monocyte adhesion.