Adsorption of inflammatory cytokines using a heparin-coated extracorporeal circuit.
Adsorption of inflammatory cytokines using a heparin-coated extracorporeal circuit.
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使用肝素涂层的体外回路吸附炎症细胞因子。
DOI：
10.1046/j.1525-1594.2002.07017.x
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发表时间：
2002
影响因子：
2.4
通讯作者：
T. Maehara
中科院分区：
文献类型：
--
作者：
M. Fujita;M. Ishihara;K. Ono;H. Hattori;A. Kurita;M. Shimizu;A. Mitsumaru;D. Segawa;K. Hinokiyama;Y. Kusama;M. Kikuchi;T. Maehara
心脏搭桥术（CPB）手术导致血浆炎性细胞因子（如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）沿着全身炎症反应增加。当使用肝素涂层体外循环回路时，CPB治疗期间的炎症反应减少。由于已知许多细胞因子、生长因子和补体与肝素相互作用，因此肝素涂层回路对炎症反应的减少可能取决于炎症细胞因子的肝素结合性质。在这项研究中，胎牛血清（FBS）中的炎性细胞因子TNF-α和IL-6与肝素-琼脂糖珠（肝素珠）柱结合，并且在加入肝素时以浓度依赖性方式竞争性抑制吸附。与IL-6相比，FBS中的TNF-α需要更高浓度的肝素（50%浓度抑制[IC 50] > 20 μ g/ml）来抑制肝素珠-柱的吸附，这可能是因为TNF-α与肝素珠之间的相互作用更强。CPB治疗后，人肝素化血液中的TNF-α和IL-6浓度显著升高。尽管肝素包被的回路上IL-6的吸附量较低（小于游离循环IL-6的6%），但显著量的TNF-α吸附到回路上（游离循环TNF-α的23.9-755%）。因此，炎性细胞因子（尤其是TNF-α）吸附到体外循环管路的肝素涂层内表面上可能是炎性反应减少的部分原因。
Cardiopulmonary bypass (CPB) surgeries cause an increase in plasma inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) along with whole-body inflammatory responses. The inflammatory responses during a CPB treatment are reduced when using a heparin-coated extracorporeal circuit. Because many cytokines, growth factors, and complements are known to interact with heparin, the reduction of inflammatory responses by a heparin-coated circuit is likely to depend on this heparin-binding nature of the inflammatory cytokines. In this study, the inflammatory cytokines, TNF-alpha and IL-6, in fetal bovine serum (FBS) bound to a heparin-agarose beads (heparin beads)-column and the adsorptions were competitively inhibited on addition of heparin in a concentration-dependent manner. TNF-alpha in FBS required a higher concentration of heparin (50% concentration inhibition [IC50] > 20microg/ml) to inhibit adsorption to the heparin beads-column compared with IL-6, probably because of a stronger interaction between TNF-alpha and heparin-beads. TNF-alpha and IL-6 concentrations in human heparinized blood significantly increased after a CPB treatment. Although the adsorbed amount of IL-6 onto the heparin-coated circuit was low (less than 6% of free circulating IL-6), a significant amount of TNF-alpha adsorbed onto the circuit (23.9-755% of free circulating TNF-alpha). Therefore, the adsorption of inflammatory cytokines, especially TNF-alpha, onto the inner heparin-coated surface of an extracorporeal circuit may partly account for a reduction in inflammatory responses.