Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T
Institute of Cancer Research, University of Trondheim, Norway.
J Exp Med. 1989 Dec 1;170(6):1859-67. doi: 10.1084/jem.170.6.1859.
We examined the cerebrospinal fluid (CF) taken on admission from 60 patients with infections caused by Neisseria meningitidis for presence of TNF-alpha, IL-1, and IL-6. TNF-alpha was detected in CF in 55 and 19% (p = 0.03), IL-1 in 50 and 15% (p = 0.05), and IL-6 in 98 and 100% of patients with meningitis and septic shock/bacteremia, respectively. The median IL-6 concentration in CF in patients with meningitis was 154 ng/ml, and in patients with septic shock/bacteremia it was 42 ng/ml (p = 0.001). The level of LPS in CF correlated with the level of TNF-alpha (r = 0.91, p less than 0.001), but not with the level of IL-1 and IL-6. CF levels of TNF-alpha, IL-1, and IL-6 correlated with each other (r = 0.34-0.54, p less than 0.01), with the protein concentration (r = 0.34-0.62, p less than 0.01) and inversely with the CF/blood glucose ratio (r = -0.34 to -0.67, p less than 0.01). Only the Il-6 level correlated with the leukocyte count (r = 0.37, p less than 0.01). In rabbits TNF-alpha, IL-1, and IL-6 activities sequentially appeared in CF within 3 h of injection of meningococcal LPS or viable meningococci, whereas the main infiltration of granulocytes started after 4 h. TNF-alpha was detected in serum at concentrations less than 1/100 of those in CF after administration of LPS into the subarachnoid space, and conversely, TNF-alpha was detected in CF at concentrations 1/100 of those in serum after intravenous injection of LPS. The results demonstrate that TNF-alpha, IL-1, and IL-6 are sequentially produced in the initial phase of the local inflammatory response caused by meningococci, and that the subarachnoid space and systemic circulation are separate compartments with respect to production of TNF-alpha, IL-1, and IL-6.
我们检测了60例因脑膜炎奈瑟菌感染入院患者的脑脊液（CF），以检测其中肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）和白细胞介素-6（IL-6）的存在情况。在脑膜炎患者和感染性休克/菌血症患者中，分别有55%和19%（p = 0.03）的脑脊液检测到TNF-α，50%和15%（p = 0.05）的脑脊液检测到IL-1，98%和100%的脑脊液检测到IL-6。脑膜炎患者脑脊液中IL-6的中位浓度为154 ng/ml，感染性休克/菌血症患者脑脊液中IL-6的中位浓度为42 ng/ml（p = 0.001）。脑脊液中脂多糖（LPS）水平与TNF-α水平相关（r = 0.91，p < 0.001），但与IL-1和IL-6水平无关。脑脊液中TNF-α、IL-1和IL-6水平相互相关（r = 0.34 - 0.54，p < 0.01），与蛋白浓度相关（r = 0.34 - 0.62，p < 0.01），与脑脊液/血糖比值呈负相关（r = -0.34至-0.67，p < 0.01）。只有IL-6水平与白细胞计数相关（r = 0.37，p < 0.01）。在兔体内，注射脑膜炎球菌LPS或活的脑膜炎球菌后3小时内，脑脊液中依次出现TNF-α、IL-1和IL-6活性，而粒细胞的主要浸润在4小时后开始。蛛网膜下腔注射LPS后，血清中检测到的TNF-α浓度不到脑脊液中浓度的确1/100，相反，静脉注射LPS后，脑脊液中检测到的TNF-α浓度为血清中浓度的1/100。结果表明，TNF-α、IL-1和IL-6在脑膜炎球菌引起的局部炎症反应的初始阶段依次产生，并且就TNF-α、IL-1和IL-6的产生而言，蛛网膜下腔和体循环是分开的隔室。
