THE EFFECTS OF HEMODIALYSIS (HD) MEMBRANES ON INTERLEUKIN-1-BETA (IL-1-BETA) PRODUCTION FROM PERIPHERAL-BLOOD MONONUCLEAR-CELLS (PBMC)

Dialysis-related symptoms are thought to be mediated by monocyte/macro phage-derived inflammatory cytokines, including interleukin 1-beta (IL -1 beta) and tumor necrosis factor alpha (TNF alpha). We investigated the effects of hemodialysis (HD) membranes on IL-1 beta production usi ng cultured peripheral blood mononuclear cells (PBMC). PBMC were stimu lated with lipopolysaccharide (LPS) and the cell content and productio n of IL-1 beta were measured by ELISA. PBMC from a single healthy dono r incubated with 5% of untreated plasma, and we found that HD patients plasma enhanced IL-1 beta production less than normal control plasma. The plasma obtained from the venous side of HD patients 15 minutes af ter starting a single HD (15-min HD plasma) did not enhance IL-1 beta production as much as the plasma from the arterial side, either before or upon completion of a single HD (pre-HD plasma, post-HD plasma). We studied IL-1 beta productivity when pre-HD plasma (arterial side) and 15-min HD plasma (venous side) were added to autologous PBMC. The IL- 1 beta production by PBMC was less when the 15-min HD plasma was added to PBMC as compared to when the pre-HD plasma was added. This reducti on tended to be greater when a dialyzer membrane used was a large-pore type made of regenerated cellulose (RC) or polymethylmetacrylate (PMM A) than with a small-pore RC membrane. After HD for 2 weeks using a sm all-pore RC membrane, the same HD patient was then treated with a larg e-pore RC membrane. The PBMC IL-1 beta production level decreased with the use of the large-pore RC as compared to the case with the small-p ore RC membranes. The present study suggests that large-pore dialyzer membranes remove middle molecules and low molecular weight proteins wh ich enhance IL-1 beta production, and that this production may be regu lated by some mechanism unrelated to complement activation.