Ossege L M, Sindern E, Voss B, Malin J P
Department of Neurology, Ruhr-University of Bochum, Germany.
J Neurol Sci. 1996 Dec;144(1-2):1-13. doi: 10.1016/s0022-510x(96)00204-3.
Meningitis is an acute inflammatory disease of the pia and arachnoid and the fluid in the subarachnoid space, in which a participation of cytokines can be expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory reactions, transforming growth factor-beta 1 (TGF beta 1) has antagonistic effects and suppresses the inflammation in the subarachnoid space. We investigated the protein concentration and mRNA expression of TNF alpha and TGF beta 1 in cerebrospinal fluid (CSF) by ELISA and intracellularly by non-radioactive in situ hybridization in 23 patients with bacterial or viral meningitis. A higher amount of both cytokines on protein and mRNA level, especially of TNF alpha, could be detected in bacterial infection. While an imbalance of both cytokines with a preponderance of TNF alpha- compared to TGF beta 1-mRNA was visible in CSF cells of patients with bacterial meningitis, a balance of TNF alpha- and TGF beta 1-mRNA or a higher expression of TGF beta 1-mRNA could be detected in viral meningitis. In the acute phase of the disease neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than lymphocytes and monocytes/macrophages, while these cell types were dominating the cytokine synthesis during the healing phase. These data indicate that immunomodulatory mechanisms take place in the CSF compartment itself, regulated by CSF cells in different but specific ways. In addition, TGF beta 1 seems to be involved in the down-regulation of the inflammatory activity and to be one factor in the cytokine network, which could contribute to a lower rate of complications and positive outcomes. Moreover this study favors the possibility to monitor the immunomodulatory mechanisms by non-radioactive in situ hybridization.
脑膜炎是软脑膜、蛛网膜及蛛网膜下腔积液的一种急性炎症性疾病，预计细胞因子会参与其中。肿瘤坏死因子-α（TNFα）促进炎症反应，而转化生长因子-β1（TGFβ1）具有拮抗作用，可抑制蛛网膜下腔的炎症。我们通过酶联免疫吸附测定（ELISA）法检测了23例细菌性或病毒性脑膜炎患者脑脊液（CSF）中TNFα和TGFβ1的蛋白浓度，并通过非放射性原位杂交法检测了细胞内的mRNA表达。在细菌感染中可检测到两种细胞因子在蛋白和mRNA水平上的含量均较高，尤其是TNFα。与TGFβ1相比，细菌性脑膜炎患者CSF细胞中TNFα占优势，两种细胞因子失衡，而在病毒性脑膜炎中可检测到TNFα和TGFβ1 mRNA平衡或TGFβ1 mRNA表达较高。在疾病急性期，中性粒细胞表达的TNFα和TGFβ1 mRNA比淋巴细胞和单核细胞/巨噬细胞更多，而在愈合期这些细胞类型主导细胞因子合成。这些数据表明免疫调节机制在CSF区室本身发生，由CSF细胞以不同但特定的方式调节。此外，TGFβ1似乎参与炎症活性的下调，是细胞因子网络中的一个因素，这可能有助于降低并发症发生率和取得良好预后。而且，本研究支持通过非放射性原位杂交监测免疫调节机制的可能性。
