Momoi T, Ono M, Takagi T, Sugiura S, Ogawa H, Saito A
Bio-Dynamics Research Institute, Nagoya, Japan.
Clin Nephrol. 1995 Nov;44 Suppl 1:S24-8.
Dialysis-related symptoms are thought to be mediated by monocyte/macrophage-derived inflammatory cytokines, including interleukin 1-beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). We investigated the effect of hemodialysis (HD) membranes on IL-1 beta production using cultured peripheral blood mononuclear cells (PBMC). PBMC were stimulated with lipopolysaccharide (LPS) and the cell content and production of IL-1 beta were measured by ELISA. PBMC from a single healthy donor 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 after 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 reduction tended to be greater when a dialyzer membrane used was a large-pore type made of regenerated cellulose (RC) or polymethylmetacrylate (PMMA) than with a small-pore RC membrane. After HD for 2 weeks using a small-pore RC membrane, the same HD patient was then treated with a large-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-pore RC membranes. The present study suggests that large-pore dialyzer membranes remove middle molecules and low molecular weight proteins which enhance IL-1 beta production, and that this production may be regulated by some mechanism unrelated to complement activation.
透析相关症状被认为是由单核细胞/巨噬细胞衍生的炎性细胞因子介导的，包括白细胞介素1-β（IL-1β）和肿瘤坏死因子α（TNFα）。我们使用培养的外周血单个核细胞（PBMC）研究了血液透析（HD）膜对IL-1β产生的影响。用脂多糖（LPS）刺激PBMC，并通过酶联免疫吸附测定（ELISA）测量细胞中IL-1β的含量和产生量。将来自单一健康供体的PBMC与5%未处理的血浆一起孵育，我们发现HD患者的血浆增强IL-1β产生的能力低于正常对照血浆。在单次HD开始15分钟后从HD患者静脉侧获得的血浆（15分钟HD血浆）增强IL-1β产生的能力不如单次HD之前或结束时动脉侧血浆（HD前血浆、HD后血浆）。我们研究了将HD前血浆（动脉侧）和15分钟HD血浆（静脉侧）添加到自体PBMC时的IL-1β产生能力。与添加HD前血浆相比，将15分钟HD血浆添加到PBMC时，PBMC产生的IL-1β较少。当使用的透析器膜是由再生纤维素（RC）或聚甲基丙烯酸甲酯（PMMA）制成的大孔型时，这种降低趋势比使用小孔径RC膜时更大。使用小孔径RC膜进行2周HD后，同一名HD患者随后使用大孔RC膜进行治疗。与使用小孔径RC膜的情况相比，使用大孔RC膜时PBMC的IL-1β产生水平降低。本研究表明，大孔透析器膜可去除增强IL-1β产生的中分子和低分子量蛋白质，并且这种产生可能受与补体激活无关的某种机制调节。
