DISSOCIATION BETWEEN BETA-2-MICROGLOBULIN AND IL-1 PRODUCTION IN HEMODIALYZED PATIENTS

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 di alysate, uremia and chronic systemic inflammation associated with enha nced monocytic cytokine production in hemodialyzed patients. Interleuk in-1 has been proposed to play a critical role in the induction of bet a-2 microglobulin synthesis and release. Methods. We examined if monoc ytes contribute to beta-2 microglobulin production upon stimulation wi th inflammatory mediators that are generated during hemodialysis and i nvestigated the production of beta-2 microglobulin by cells from patie nts, 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 i ncreased levels of beta-2 microglobulin upon stimulation by IL-1, TNF alpha, C5a and LPS. Increased levels of beta-2 microglobulin were asso ciated with increased levels of beta-2 microglobulin mRNA. Before dial ysis session, 20-60% of circulating CD14(+) monocytes from patients co ntained IL-1. At the time when maximal IL-1 production was detected, w e showed by RT-PCR increased transcription of IL-1 gene in patients' m onocytes. We observed that monocytes from patients with amyloidosis co ntained 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. Ou r data indicated that chronic inflammation, as demonstrated by increas ed intracellular IL-1 expression, is not associated with increased pro duction of beta-2 microglobulin by monocytes from patients on hemodial ysis.