Matusevicius D, Navikas V, Söderström M, Xiao B G, Haglund M, Fredrikson S, Link H
Division of Neurology, Karolinska Institute, Huddinge Hospital, Sweden.
J Neuroimmunol. 1996 May;66(1-2):115-23. doi: 10.1016/0165-5728(96)00032-x.
Lymphotoxin-alpha (LT-alpha) and tumour necrosis factor-alpha (TNF-alpha) promote inflammation in autoimmune diseases and have been detected in the multiple sclerosis (MS) brain lesions and blood, suggesting these cytokines are also present in the cerebrospinal fluid (CSF). To study this, mononuclear cells (MNC) were examined for transcripts of LT-alpha and TNF-alpha, using in situ hybridization (ISH) with synthetic oligonucleotide probes. Most patients with MS had LT-alpha and TNF-alpha mRNA-expressing MNC in their CSF at mean frequencies of about 1/2800 cells for both cytokines. Numbers were dramatically higher than in the paired blood specimens. Control patients with other inflammatory neurological diseases (OIND) also had LT-alpha and TNF-alpha mRNA-expressing cells in CSF but at mean frequencies of only 1/36,000 and 1/18,000 cells, respectively. In blood, levels were similar in OIND and MS. To elucidate the influence of myelin antigen stimulation on LT-alpha and TNF-alpha expression, MNC were cultivated with or without myelin basic protein. Strongly elevated levels of MBP-reactive TNF-alpha mRNA-expressing cells were detected in the MS patients' CSF, in particular when examined during clinical exacerbations, as well as MBP-reactive LT-alpha mRNA-expressing MNC. No such patterns were observed in the OIND controls. The strong accumulation of LT-alpha- and TNF-alpha-producing cells and of MBP-reactive LT-alpha and TNF-alpha mRNA-positive cells in the immediate vicinity of the demyelinating process in MS patients implicates a role of these cytokines in the development of MS.
淋巴毒素-α（LT-α）和肿瘤坏死因子-α（TNF-α）在自身免疫性疾病中促进炎症反应，并且已在多发性硬化症（MS）的脑病变和血液中检测到，这表明这些细胞因子也存在于脑脊液（CSF）中。为了对此进行研究，使用合成寡核苷酸探针通过原位杂交（ISH）检测单核细胞（MNC）中LT-α和TNF-α的转录本。大多数MS患者的脑脊液中有表达LT-α和TNF-α mRNA的MNC，两种细胞因子的平均频率约为1/2800个细胞。其数量显著高于配对的血液标本。患有其他炎性神经系统疾病（OIND）的对照患者脑脊液中也有表达LT-α和TNF-α mRNA的细胞，但平均频率分别仅为1/36,000和1/18,000个细胞。在血液中，OIND患者和MS患者的水平相似。为了阐明髓鞘抗原刺激对LT-α和TNF-α表达的影响，将MNC在有或没有髓鞘碱性蛋白的情况下进行培养。在MS患者的脑脊液中检测到表达MBP反应性TNF-α mRNA的细胞水平显著升高，特别是在临床病情加重期间进行检查时，以及表达MBP反应性LT-α mRNA的MNC。在OIND对照中未观察到这种模式。MS患者脱髓鞘过程紧邻区域中产生LT-α和TNF-α的细胞以及MBP反应性LT-α和TNF-α mRNA阳性细胞的大量积累表明这些细胞因子在MS的发展中起作用。
