París M M, Friedland I R, Ehrett S, Hickey S M, Olsen K D, Hansen E, Thonar E J, McCracken G H
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
J Infect Dis. 1995 Jan;171(1):161-9. doi: 10.1093/infdis/171.1.161.
Intracisternal or intraarticular inoculation of rabbit recombinant interleukin (IL)-1 beta and rabbit tumor necrosis factor-alpha combined with IL-1 receptor antagonist (IL-1RA) and soluble tumor necrosis factor receptor (sTNFR), respectively, produced significantly less inflammation in rabbits than after inoculation of these cytokines alone. In contrast, when Haemophilus influenzae type b (Hib) or Hib lipooligosaccharide (LOS) was given intraarticularly with IL-1RA, sTNFR, or the combination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation. In the experimental meningitis model, IL-1RA and sTNFR did not significantly reduce the meningeal inflammatory response associated with intracisternal inoculation of Hib LOS. These data indicate that specific cytokine inhibitors (sTNFR and IL-1RA) may not be effective in modulating inflammation induced by a broad inflammatory stimulus such as gram-negative bacteria or their products and suggest caution in using them to treat these infectious conditions in humans.
分别将兔重组白细胞介素（IL）-1β和兔肿瘤坏死因子-α与IL-1受体拮抗剂（IL-1RA）和可溶性肿瘤坏死因子受体（sTNFR）进行脑池内或关节内接种，与单独接种这些细胞因子相比，在兔体内产生的炎症明显更少。相比之下，当将b型流感嗜血杆菌（Hib）或Hib脂寡糖（LOS）与IL-1RA、sTNFR或两者组合进行关节内给药时，滑膜炎症和软骨蛋白聚糖降解没有明显或一致的调节作用。在实验性脑膜炎模型中，IL-1RA和sTNFR并没有显著降低与脑池内接种Hib LOS相关的脑膜炎症反应。这些数据表明，特异性细胞因子抑制剂（sTNFR和IL-1RA）可能无法有效调节由革兰氏阴性菌或其产物等广泛炎症刺激所诱导的炎症，并提示在人类使用它们治疗这些感染性疾病时应谨慎。
