Hypervolemia-Induced immune disturbances do not involve IL-1ß but IL-6 and IL-10 activation in Haemodialysis patients

Abstract

Dysregulated fluid homeostasis is frequent in haemodialysis (HD) patients and is linked to inflammation which may be elicited by endotoxemia. The impact of hypervolemia on immune cells has not been studied in detail. Therefore, we analysed the hypervolemic activation of peripheral blood mononuclear cells (PBMCs) in HD with special focus on the NLRP3 inflammasome response. First, 45 HD were included in the observational study. Immune parameters including cell counts, caspase-1, oxidative stress, cytokine gene expression and serum analysis (IL-1ß, IL-6, IL-10) were all measured at two time points. Fluid status was evaluated by electrical bioimpedance vector analysis, defining hypervolemia (H) as >75 vector percentile. Then, 17 patients were classified as hypervolemic (H-HD), 19 as normovolemic (N-HD) and 9 failed to meet the inclusion criteria. Monocytes were elevated and lymphocytes were decreased by hypervolemia. NLRP3 inflammasome components, caspase-1 and IL-1ß expression were not statistically different between the two groups. Serum IL-6 levels were significantly elevated in H-HD. IL-10 mRNA transcripts were elevated by 2-fold in H-HD but were not efficiently translated. We conclude that the NLRP3 inflammasome is not activated by hypervolemia thus refuting the thesis that endotoxemia may be a main driver for inflammation in H-HD. Nevertheless, inflammation is generally higher in H-HD compared to N-HD patients and is not sufficiently balanced by anti-inflammatory mechanisms.