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Response of peripheral blood mononuclear cells in hemodialyzed patients against endotoxin and muramyldipeptide
Tatsuya Nakatani1, Kenji Tsuchida, Kazunobu Sugimura
1Department of Urology and Devision of Artificial Kidney, Osaka City University Medical School, Abeno-ku, Osaka City 545-8586, Japan. nakatani@msic.med.osaka-cu.ac.jp
Abstract:
Microbial fragments of endotoxin (ET) and peptidoglycan (PG) are recognized as pyrogen in dialysate. The aim of this study was to evaluate the effect of contaminated dialysate on peripheral blood mononuclear cells (PBMC) in hemodialyzed patients by measuring production of interleukine 1-beta (IL-1beta) in vitro. Venous blood was withdrawn before dialysis session. The effects of a dialysis membrane, a magnitude of dialysate contamination and a duration of hemodialysis were studied. PBMC was stimulated by the addition of water containing either ET or muramyldipeptide (MDP), the minimum biological activated fragment of PG, or ET+MDP. IL-1beta production of PBMC stimulated by ET or ET+MDP in patients on hemodialysis using a polysulfon (PS) membrane was significantly lower than those using a cuprammonium-rayon (CU) membrane, ethylenevinylalcohol (EVAL) membrane, polymethylmetacrylate (PMMA) membrane, respectively. Among patients on the PS membranes, those who were exposed to dialysate with higher pyrogen contamination had lower PBMC cytokine production than those dialyzed with ultrapure dialysate. Response of PBMC in patients against ET+MDP stimulant decreased with duration of dialysis treatment. This suggested that chronic exposure to ET or MDP during hemodialysis treatment, might cause a tolerance against ET and ET+MDP in PBMC.
Insights
Dialysate pyrogens like endotoxin (ET) and peptidoglycan (PG) fragments can affect hemodialysis patients. Chronic exposure may lead to reduced immune cell responses, suggesting tolerance development.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Microbial fragments, including endotoxin (ET) and peptidoglycan (PG), act as pyrogens in dialysis fluid.
- Hemodialysis patients may be exposed to these pyrogens, potentially impacting their immune system.
- Interleukin-1 beta (IL-1beta) is a key cytokine involved in inflammatory responses.
Purpose of the Study:
- To investigate the impact of contaminated dialysate on peripheral blood mononuclear cells (PBMC) in hemodialysis patients.
- To measure the in vitro production of IL-1beta by PBMCs in response to pyrogens.
- To assess the influence of dialysis membrane type, dialysate contamination level, and hemodialysis duration.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) were isolated from hemodialysis patients before dialysis.
- PBMCs were stimulated in vitro with endotoxin (ET), muramyldipeptide (MDP - a PG fragment), or both.
- IL-1beta production was measured, comparing responses across different dialysis membranes (PS, CU, EVAL, PMMA), contamination levels, and dialysis durations.
Main Results:
- PBMC IL-1beta production stimulated by ET or ET+MDP was significantly lower with polysulfon (PS) membranes compared to CU, EVAL, and PMMA membranes.
- Patients on PS membranes exposed to higher pyrogen contamination showed reduced PBMC cytokine production versus those using ultrapure dialysate.
- The response of PBMCs to ET+MDP stimulation decreased with increasing duration of hemodialysis treatment.
Conclusions:
- Dialysis membrane material influences PBMC response to pyrogens.
- Higher dialysate pyrogen contamination and longer dialysis duration are associated with diminished PBMC cytokine production.
- Chronic exposure to ET and MDP during hemodialysis may induce tolerance in PBMCs, reducing their inflammatory response.
