Burroughs M H, Tsenova-Berkova L, Sokol K, Ossig J, Tuomanen E, Kaplan G
Laboratory of Cellular Physiology & Immunology, Rockefeller University, New York, N.Y. 10021, USA.
Microb Pathog. 1995 Oct;19(4):245-55. doi: 10.1016/s0882-4010(95)90299-6.
In experimental bacterial meningitis in rabbits, the inflammatory process is largely mediated by cytokines such as IL-1 and TNF-alpha. Since thalidomide has been shown to inhibit TNF-alpha production, experiments were carried out to determine whether the drug can modulate the inflammatory response to either lysates of H. influenzae (gram negative) or heat killed S. pneumoniae (gram positive) in rabbits. The introduction of a lysate of H. influenzae into the CSF of rabbits causes a very acute inflammatory response, as indicated by a rapid increase in TNF-alpha levels in the CSF and a concomitantly rapid leukocytosis. In contrast, the introduction of heat killed S. pneumoniae, induces a more indolent inflammatory response which also wanes more slowly. Thalidomide treatment reduces TNF-alpha production in both experimental systems, but has a greater effect on the more indolent gram positive inflammatory response in which peak TNF-alpha levels in the CSF are reduced by > 50%. Also, a sustained inhibition of leukocytosis is observed in the inflammatory response to heat-killed gram positive bacteria. In meningeal inflammation induced by the Gram negative lysate, treatment with thalidomide results in only a 29% inhibition of TNF-alpha release into the CSF. In contrast to the drug effect on TNF-alpha, thalidomide treatment does not significantly affect IL-1 levels in these models of rabbit bacterial meningitis.
在兔实验性细菌性脑膜炎中，炎症过程很大程度上由细胞因子如白细胞介素-1和肿瘤坏死因子-α介导。由于已证明沙利度胺可抑制肿瘤坏死因子-α的产生，因此进行了实验以确定该药物是否能调节兔对流感嗜血杆菌（革兰氏阴性）裂解物或热灭活肺炎链球菌（革兰氏阳性）的炎症反应。将流感嗜血杆菌裂解物引入兔脑脊液会引起非常急性的炎症反应，脑脊液中肿瘤坏死因子-α水平迅速升高以及随之而来的白细胞迅速增多表明了这一点。相比之下，引入热灭活肺炎链球菌会诱导更缓慢的炎症反应，且消退也更慢。沙利度胺治疗在两个实验系统中均降低了肿瘤坏死因子-α的产生，但对更缓慢的革兰氏阳性炎症反应影响更大，其中脑脊液中肿瘤坏死因子-α的峰值水平降低了>50%。此外，在对热灭活革兰氏阳性菌的炎症反应中观察到白细胞增多的持续抑制。在革兰氏阴性裂解物诱导的脑膜炎症中，沙利度胺治疗仅使脑脊液中肿瘤坏死因子-α的释放抑制了29%。与该药物对肿瘤坏死因子-α的作用相反，沙利度胺治疗在这些兔细菌性脑膜炎模型中对白细胞介素-1水平没有显著影响。
