Lo W D, Chen R, Boue D R, Stokes B T
Department of Pediatrics, Ohio State University, Children's Hospital, Columbus 43205, USA.
Brain Res. 1998 Aug 17;802(1-2):175-83. doi: 10.1016/s0006-8993(98)00600-3.
Inhibition of the host's neutrophil response has been proposed as one means to reduce tissue damage in acute inflammation. If this approach can be applied in acute central nervous system (CNS) infection, the long-term morbidity, which occurs in CNS infection, might be reduced. Previous studies in models of CNS infection yielded conflicting results whether neutrophil depletion might be protective. To determine whether neutrophil depletion reduces tissue necrosis and cerebrovascular injury in experimental bacterial cerebritis, we depleted circulating neutrophils with an IgM monoclonal antibody, RP3, given after the start of the infection. RP3 treatment successfully depleted circulating neutrophils and reduced the extent of neutrophil influx into the cerebritis region. The extent of tissue necrosis, measured histologically, and the regional increase of blood-brain barrier (BBB) permeability were not inhibited by neutrophil depletion, and in animals treated with RP3 alone, the extent of tissue necrosis and BBB permeability tended to be larger than in S. aureus inoculated controls. We conclude that host neutrophils do not add to the tissue and cerebrovascular damage created by the intracerebral inoculation of a pathogenic bacteria, and the neutrophils serve to diminish local damage in the setting of a cerebritis.
抑制宿主的中性粒细胞反应已被提出作为减少急性炎症中组织损伤的一种手段。如果这种方法能够应用于急性中枢神经系统（CNS）感染，那么CNS感染中出现的长期发病率可能会降低。先前在CNS感染模型中的研究对于中性粒细胞耗竭是否具有保护作用产生了相互矛盾的结果。为了确定中性粒细胞耗竭是否能减少实验性细菌性脑脓肿中的组织坏死和脑血管损伤，我们在感染开始后给予一种IgM单克隆抗体RP3以耗竭循环中的中性粒细胞。RP3治疗成功地耗竭了循环中的中性粒细胞，并减少了中性粒细胞流入脑脓肿区域的程度。组织学测量的组织坏死程度以及血脑屏障（BBB）通透性的区域增加并未因中性粒细胞耗竭而受到抑制，并且在仅用RP3治疗的动物中，组织坏死程度和BBB通透性往往比接种金黄色葡萄球菌的对照组更大。我们得出结论，宿主中性粒细胞不会加重脑内接种病原菌所造成的组织和脑血管损伤，并且中性粒细胞在脑脓肿的情况下有助于减轻局部损伤。
