Bacterial DNA prolongs the survival of inflamed mononuclear cells in haemodialysis patients.
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.
Navarro
Maria Dolores
MD
Servicio de Nefrología, Hospital Universitario Reina Sofía, Avda Menendez Pidal s/n, Córdoba 14004. Spain. mariad.navarro.sspa@juntadeandalucia.es
Carracedo
Julia
J
Ramírez
Rafael
R
Madueño
Juan Antonio
JA
Merino
Ana
A
Rodríguez
Mariano
M
Martín-Malo
Alejandro
A
Aljama
Pedro
P
D000328:Adult; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002908:Chronic Disease; D004269:DNA, Bacterial / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation; D007674:Kidney Diseases / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D004269:DNA, Bacterial