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.

Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6

“…Most likely, this is at least partially caused by imbalanced anti-inflammatory mechanisms. The most prominent member of the anti-inflammatory arsenal is IL-10, and in line with the theoryinflammation is followed by anti-inflammation-we confirmed an earlier observation indicating higher IL-10 mRNA expression in hypervolemia [4].…”

“…Therefore, the inflammatory burden of hypervolemic chronic kidney disease patients is very high. Several authors reported higher IL-6 serum levels in overhydrated 2 of 14 dialysis patients [2][3][4]. Further, it is widely acknowledged that IL-6 is linked to cardiovascular diseases, in particular to chronic coronary syndrome [5], atherosclerosis [6], and hypertension [7] in chronic kidney disease.…”

A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+T cell profile

“…It has been shown that high levels of TNFα in COVID-19 could induce downstream activation of T H1 cells and block the final step of cT FH differentiation (Kaneko et al, 2020). This skewing may contribute to the delay observed in B cell responses to SARS-CoV-2 vaccination due to an insufficient feedback inhibition of pro-inflammatory cytokines (Perianayagam et al, 2002; Ulrich et al, 2020). The third dose was characterized in HD by the normalization of the effector function profile compared to the CI.…”

Immune Dysfunction in Uremia 2020

“…The combination of hypervolemia and inflammation, both independent risk factors for mortality, can lead to a cumulative risk profile [85]. Ulrich et al [86] assessed the hypervolemic activation of peripheral blood mononuclear cells of HD patients with special emphasis on the NLRP3 inflammasome response. They found that the NLRP3 inflammasome is not activated by hypervolemia, suggesting that endotoxemia is not a main driver for inflammation in hypervolemic HD patients.…”