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Dissociation between beta-2 microglobulin and IL-1 production in hemodialyzed patients
M P Carreno1, Y Rousseau, J L Poignet
1INSERM U430, Paris, France.
Background:
beta-2 microglobulin is predominant in amyloid deposits in patients undergoing long term hemodialysis. Amyloid accumulation has been ascribed to dialysis membranes, endotoxin contamination of the dialysate, uremia and chronic systemic inflammation associated with enhanced monocytic cytokine production in hemodialyzed patients. Interleukin-1 has been proposed to play a critical role in the induction of beta-2 microglobulin synthesis and release.
Methods:
We examined if monocytes contribute to beta-2 microglobulin production upon stimulation with inflammatory mediators that are generated during hemodialysis and investigated the production of beta-2 microglobulin by cells from patients, with and without clinical signs of amyloidosis, at the time when patients' monocytes contained maximal intracellular accumulation of IL-1.
Results:
We demonstrated that only monocytes are able to release increased levels of beta-2 microglobulin upon stimulation by IL-1, TNF alpha, C5a and LPS. Increased levels of beta-2 microglobulin were associated with increased levels of beta-2 microglobulin mRNA. Before dialysis session, 20-60% of circulating CD14+ monocytes from patients contained IL-1. At the time when maximal IL-1 production was detected, we showed by RT-PCR increased transcription of IL-1 gene in patients' monocytes. We observed that monocytes from patients with amyloidosis contained higher amounts of IL-1 as compared to monocytes from patients without clinical signs of amyloidosis, but could not secrete increased amounts of beta-2 microglobulin upon LPS-stimulation.
Conclusions:
Our data indicated that chronic inflammation, as demonstrated by increased intracellular IL-1 expression, is not associated with increased production of beta-2 microglobulin by monocytes from patients on hemodialysis.
Insights
Chronic inflammation in hemodialysis patients does not increase beta-2 microglobulin production by monocytes, despite elevated intracellular Interleukin-1 (IL-1). This suggests inflammation alone doesn't drive beta-2 microglobulin release in these patients.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Beta-2 microglobulin amyloidosis is common in long-term hemodialysis patients.
- Amyloid accumulation is linked to dialysis factors and chronic inflammation.
- Interleukin-1 (IL-1) is implicated in beta-2 microglobulin synthesis.
Purpose of the Study:
- To investigate monocyte contribution to beta-2 microglobulin production during hemodialysis.
- To examine beta-2 microglobulin production in patients with and without amyloidosis, correlating with IL-1 levels.
Main Methods:
- Monocyte stimulation with inflammatory mediators (IL-1, TNF alpha, C5a, LPS).
- Measurement of beta-2 microglobulin and its mRNA levels.
- Analysis of intracellular IL-1 in monocytes via RT-PCR.
Main Results:
- Monocytes release increased beta-2 microglobulin upon stimulation; mRNA levels correlate.
- Elevated intracellular IL-1 is found in monocytes before dialysis.
- Monocytes from amyloidosis patients have more IL-1 but do not secrete more beta-2 microglobulin upon LPS stimulation.
Conclusions:
- Increased intracellular IL-1 (chronic inflammation marker) is not directly associated with elevated beta-2 microglobulin production by monocytes in hemodialysis patients.