Lonnemann G, Koch K M, Shaldon S, Dinarello C A
Division of Geographic Medicine and Infectious Diseases, New England Medical Center Hospitals, Boston, MA 02111.
J Lab Clin Med. 1988 Jul;112(1):76-86.
Interleukin-1 (IL-1) is a polypeptide cytokine predominantly produced by monocytes in response to injury or infection. Effects of IL-1 such as fever, acute phase protein synthesis, hypotension, and loss of body mass are complications of hemodialysis. Endotoxin-contaminated dialysate fluid, sodium acetate as a dialysate buffer, and activated complement can induce IL-1 during hemodialysis. In the present study, we investigated the intrinsic property of hemodialysis membranes to stimulate human blood mononuclear cells (MNC) to produce IL-1. Incubation of MNC on sheets of two commonly used hemodialysis membranes, regenerated cellulose (RC) and polyacrylonitrile (PAN) resulted in significant induction of IL-1 in the absence of endotoxin or complement. Production of intracellular and extracellular IL-1 was greater in MNC exposed to PAN compared with RC (p less than 0.01). Similar results were obtained when MNC were exposed to strips of hemodialysis membranes in rotating tubes. However, compared with RC, PAN binds significant amounts of human IL-1. In a model of in vitro hemodialysis, radiolabeled recombinant human IL-1 was added to the blood compartment of a PAN and a RC dialyzer. Forty percent of radiolabeled IL-1 bound to the PAN dialyzer membrane compared with 10% to the membrane of a RC dialyzer. In addition, 22% of radiolabeled IL-1 was found in the dialysate compartment of a PAN dialyzer after 1 hour whereas 1% was found in the dialysate side of a RC dialyzer; these results were confirmed by measuring bioactivity of IL-1. These studies demonstrate the intrinsic property of hemodialysis membranes to stimulate human IL-1 production; in addition they establish that dialysis membranes differ in their ability to bind and clear IL-1.
白细胞介素-1（IL-1）是一种多肽细胞因子，主要由单核细胞在受到损伤或感染时产生。IL-1的作用如发热、急性期蛋白合成、低血压和体重减轻是血液透析的并发症。内毒素污染的透析液、作为透析液缓冲剂的醋酸钠以及活化补体可在血液透析过程中诱导IL-1产生。在本研究中，我们调查了血液透析膜刺激人血单核细胞（MNC）产生IL-1的内在特性。将MNC培养在两种常用的血液透析膜——再生纤维素（RC）和聚丙烯腈（PAN）片上，在无内毒素或补体的情况下可显著诱导IL-1产生。与RC相比，暴露于PAN的MNC中细胞内和细胞外IL-1的产生量更高（p小于0.01）。当MNC在旋转管中暴露于血液透析膜条时也获得了类似结果。然而，与RC相比，PAN结合大量人IL-1。在体外血液透析模型中，将放射性标记的重组人IL-1添加到PAN和RC透析器的血液腔室中。40%的放射性标记IL-1与PAN透析器膜结合，而与RC透析器膜结合的为10%。此外，1小时后在PAN透析器的透析液腔室中发现22%的放射性标记IL-1，而在RC透析器的透析液侧发现1%；通过测量IL-1的生物活性证实了这些结果。这些研究证明了血液透析膜刺激人IL-1产生的内在特性；此外还证实透析膜在结合和清除IL-1的能力方面存在差异。
