BACKGROUND: Chronic kidney disease (CKD) patients show evidence of chronic inflammation with mononuclear cell activation which is mainly caused by uraemia itself and is exacerbated by haemodialysis. Small fragments of bacterial DNA (DNAb) are ubiquitous contaminants, which are capable of passing through dialyser membranes causing the stimulation of cells of the immune system. The aim of this study was to evaluate whether DNAb contamination may have an effect on apoptosis of activated monocytes from CKD-5 patients. METHODS: To test the ability of DNAb to stimulate the inflammatory response, mononuclear cells from 10 chronic kidney disease patients who had not begun haemodialysis (ND-CKD-5) and 10 patients undergoing regular dialysis (HD) were cultured in the presence and absence of DNAb. Ten healthy subjects were used as controls. RESULTS: The percentage of IL-1beta cells was higher in HD patients than in ND-CKD-5 (33.9 +/- 3.0% vs 20.0 +/- 2.3%, P < 0.001) and controls (9.4 +/- 2.1%, P < 0.001). The presence of DNAb induced an increase in the percent of cells expressing IL-1beta in controls, ND-CKD5 and HD patients. In addition, the DNAb also increased the release of cytokines in all groups, the effect was more marked in ND-CKD5 and HD than in controls. DNAb only inhibited apoptosis of activated mononuclear cells from, ND-CKD (17.5 +/- 2.8% vs 12.3 +/- 2.6%, P < 0.01) and HD patients (27 +/- 2.5% vs 14.6 +/- 2.9%, P < 0.01). CONCLUSIONS: DNAb enhances cytokine production and promotes the survival of inflammatory mononuclear cells from CKD patients. These results strongly suggest that DNAb fragments play an important role in maintaining chronic inflammation in patients on haemodialysis.
BACKGROUND:Chronic kidney disease (CKD) patients show evidence of chronic inflammation with mononuclear cell activation which is mainly caused by uraemia itself and is exacerbated by haemodialysis. Small fragments of bacterial DNA (DNAb) are ubiquitous contaminants, which are capable of passing through dialyser membranes causing the stimulation of cells of the immune system. The aim of this study was to evaluate whether DNAb contamination may have an effect on apoptosis of activated monocytes from CKD-5 patients. METHODS: To test the ability of DNAb to stimulate the inflammatory response, mononuclear cells from 10 chronic kidney diseasepatients who had not begun haemodialysis (ND-CKD-5) and 10 patients undergoing regular dialysis (HD) were cultured in the presence and absence of DNAb. Ten healthy subjects were used as controls. RESULTS: The percentage of IL-1beta cells was higher in HDpatients than in ND-CKD-5 (33.9 +/- 3.0% vs 20.0 +/- 2.3%, P < 0.001) and controls (9.4 +/- 2.1%, P < 0.001). The presence of DNAb induced an increase in the percent of cells expressing IL-1beta in controls, ND-CKD5 and HDpatients. In addition, the DNAb also increased the release of cytokines in all groups, the effect was more marked in ND-CKD5 and HD than in controls. DNAb only inhibited apoptosis of activated mononuclear cells from, ND-CKD (17.5 +/- 2.8% vs 12.3 +/- 2.6%, P < 0.01) and HDpatients (27 +/- 2.5% vs 14.6 +/- 2.9%, P < 0.01). CONCLUSIONS: DNAb enhances cytokine production and promotes the survival of inflammatory mononuclear cells from CKD patients. These results strongly suggest that DNAb fragments play an important role in maintaining chronic inflammation in patients on haemodialysis.
Authors: Keiichi Sumida; Zhongji Han; Chi-Yang Chiu; Tahliyah S Mims; Amandeep Bajwa; Ryan T Demmer; Susmita Datta; Csaba P Kovesdy; Joseph F Pierre Journal: Front Cell Infect Microbiol Date: 2022-05-03 Impact factor: 6.073