Nagai Miho, Hirayama Kouichi, Ebihara Itaru, Higuchi Takashi, Imaizumi Masahiro, Maruyama Hiroshi, Miyamoto Yasunori, Kakita Tomoko, Ogawa Yujiro, Fujita Shogo, Shimohata Homare, Kobayashi Masaki
Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan.
Ther Apher Dial. 2011 Aug;15(4):342-8. doi: 10.1111/j.1744-9987.2011.00966.x.
Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8 ± 230.5 pg/mL) than in controls (84.1 ± 28.7 pg/mL, P = 0.043). Between 11 survivors and 10 non-survivors, there was no significant difference in the serum TWEAK levels before the DHP-PMX therapy. During DHP-PMX therapy, however, the serum TWEAK levels were significantly increased in non-survivors (142.2 ± 88.1 pg/mL to 399.0 ± 307.1 pg/mL, P = 0.022). There was a significant correlation between the serum TWEAK levels and white blood cell counts (r = 0.393, P < 0.001), platelet counts (r = 0.418, P < 0.001), or serum CRP levels (r = 0.259, P = 0.029), but there was no correlation between the serum TWEAK levels and blood pressure. The serum TWEAK levels were also correlated with the ratio of angiopoietin-2 to -1 (r = 0.464, P < 0.001). TWEAK may be a suitable marker of disease severity and mortality in septic patients, and TWEAK levels may be associated with vascular permeability via angiopoietin balance.
毛细血管通透性是所有器官床微循环中受到严格调控的一个特征。在脓毒症中，这一特征会发生根本性改变。我们之前报道过脓毒性休克患者血清血管生成素-2水平升高，并对这些患者体内介导血管生成和炎症反应的肿瘤坏死因子（TNF）相关凋亡弱诱导因子（TWEAK）进行了研究。采用酶联免疫吸附测定法检测了20例脓毒性休克患者（均接受多黏菌素B固定纤维柱直接血液灌流治疗）和20例非脓毒症对照者的血清TWEAK水平。脓毒性休克患者的TWEAK水平（192.8±230.5 pg/mL）高于对照组（84.1±28.7 pg/mL，P = 0.043）。在11名幸存者和10名非幸存者之间，多黏菌素B固定纤维柱直接血液灌流治疗前血清TWEAK水平无显著差异。然而，在多黏菌素B固定纤维柱直接血液灌流治疗期间，非幸存者的血清TWEAK水平显著升高（从142.2±88.1 pg/mL升至399.0±307.1 pg/mL，P = 0.022）。血清TWEAK水平与白细胞计数（r = 0.393，P < 0.001）、血小板计数（r = 0.418，P < 0.001）或血清CRP水平（r = 0.259，P = 0.029）之间存在显著相关性，但血清TWEAK水平与血压之间无相关性。血清TWEAK水平还与血管生成素-2与-1的比值相关（r = 0.464，P < 0.001）。TWEAK可能是脓毒症患者疾病严重程度和死亡率的合适标志物，且TWEAK水平可能通过血管生成素平衡与血管通透性相关。
