Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4

Hypervolemia is associated with inflammation in hemodialysis (HD) patients. How hypervolemia triggers inflammation is not entirely known. We initiated a cross-sectional study enrolling 40 hemodialysis patients who were categorized into normovolemic (N; 23) and hypervolemic (H; 17) groups by bioimpedance measurement. A caspase activity assay in combination with a specific caspase-4 inhibitor was used to detect caspase-4 activity in isolated peripheral blood mononuclear cells (PBMCs). Transcription factors RelA (pS529) and RelB (pS552) were analyzed by phospho-flow cytometry. Serum endotoxins were detected by an amebocyte lysate-based assay, and IL-6 (interleukin-6) and TNF-α (Tumor necrosis factor-α) gene expression were detected using the ELISA technique. Hypervolemic patients were older, more frequently had diabetes and showed increased CRP and IL-6 levels. Caspase-4 activity, which is linked to intracellular endotoxin detection, was significantly elevated in H patients. While the frequency of RelA-expressing immune cells and the expression density in these cells did not differ, the monocytic frequency of cells positively stained for RelB (pS552) was significantly decreased in H patients. Increased caspase-4 activity in H patients may indicate a cause of inflammation in H patients. The post-translational modification of RelB (pS552) is linked to downregulation of NF-kB activity and may indicate the resolution of inflammation, which is more distinct in N patients compared to H patients. Therefore, both higher inflammatory loads and lower inflammatory resolution capacities are characteristics of H patients.