Mustafa M M, Ramilo O, Olsen K D, Franklin P S, Hansen E J, Beutler B, McCracken G H
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
J Clin Invest. 1989 Oct;84(4):1253-9. doi: 10.1172/JCI114292.
Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 10(7) CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h. Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNF alpha antibodies given IC with 20 ng Hib LOS or 2 X 10(6) CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response.
肿瘤坏死因子（TNF）可能在细菌性脑膜炎期间介导中枢神经系统损伤中起作用。在用b型流感嗜血杆菌（Hib）脂寡糖（LOS）诱导脑膜炎的兔脑脊液中，在脑池内（IC）注射20 ng Hib LOS后45分钟首次检测到TNF活性，75分钟后首次出现白细胞（WBC）。IC后120分钟观察到TNF活性峰值（45 ng/ml），并持续5小时。当使用1 - 2×10⁷CFU的Hib诱导脑膜炎时，脑脊液TNF活性峰值与20 ng Hib LOS后的峰值相当，但活性持续14小时。在IC Hib LOS前1小时或同时静脉注射地塞米松（DXM）（1 mg/kg）可显著降低TNF活性和脑膜炎症。将山羊抗人TNFα抗体与20 ng Hib LOS或2×10⁶CFU的Hib一起IC注射，导致脑脊液TNF浓度显著降低，这也与Hib LOS接种动物的脑膜炎症减轻有关。我们得出结论，TNF参与介导与Hib实验性脑膜炎相关的脑膜炎症，并且在Hib LOS之前或同时给予DXM可抑制脑脊液TNF产生并调节脑膜炎症反应。
