Ramilo O, Sáez-Llorens X, Mertsola J, Jafari H, Olsen K D, Hansen E J, Yoshinaga M, Ohkawara S, Nariuchi H, McCracken G H
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
J Exp Med. 1990 Aug 1;172(2):497-507. doi: 10.1084/jem.172.2.497.
Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.
尽管先前在兔和大鼠中使用人类细胞因子的研究已提供证据表明肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）参与了脑膜炎症级联反应，但几组研究人员获得的结果并不一致，有时甚至相互矛盾。在本研究中，将同源细胞因子应用于兔脑膜炎模型。脑池内注射10²-10⁵国际单位纯化的兔TNF-α（RaTNF-α）可引起显著的脑脊液（CSF）炎症。脑池内接种5-200纳克兔重组IL-1β（rrIL-1β）后也观察到类似反应。这两种介质与它们的特异性抗体预孵育后，脑脊液炎症反应几乎完全受到抑制。在b型流感嗜血杆菌脂寡糖诱导的脑膜炎动物中，脑池内注射抗rrIL-1β、抗RaTNF-α或两者均导致脑膜炎症的显著调节。同时注射10³国际单位的RaTNF-α和5纳克的rrIL-1β导致协同炎症反应，与单独给予每种细胞因子相比，白细胞进入脑脊液的速度更快且显著增加。这些数据为TNF-α和IL-1β在脑膜炎症初始事件中的重要作用提供了证据。
