Eckersall P D, Gow J W, McComb C, Bradley B, Rodgers J, Murray M, Kennedy P G
Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Bearsden Rd, G61 1QH, Glasgow, UK.
Parasitol Int. 2001 Mar;50(1):15-26. doi: 10.1016/s1383-5769(00)00065-9.
Stimulation of the acute phase response during infection of mice with Trypanosoma brucei brucei (T. b. brucei) was investigated in an experimental model of the post-treatment reactive encephalopathy (PTRE), a common side-effect of anti-trypanosome therapy. Plasma levels of the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid P (SAP) increased by day 7 post-infection, but by day 20 had fallen to an intermediate level. This was accompanied by induction of the cytokines, interleukin (IL)-6 and tumour necrosis factor-alpha (TNFalpha) in both liver and brain. Treatment of mice on day 21 with a subcurative dose of diminazene aceturate (Berenil), a procedure known to induce a mild PTRE, cleared the parasite from the circulation with plasma APP and liver expression of mRNA for IL-6 and TNFalpha returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFalpha was detected in the brains of animals with developing PTRE although TNFalpha was not significantly greater than in the control group. A further subcurative dose of Berenil, leading to a more severe PTRE, was associated with elevated serum concentrations of Hp and SAP, increased TNFalpha mRNA in the liver and detectable IL-6 and TNFalpha mRNA in the brain. mRNA for IL-1alpha was expressed in brain and liver samples from all animals. A severe PTRE caused a systemic acute phase response which was not apparent with a mild PTRE. The pattern of cytokine mRNA induction was similar following both drug treatments. However, the difference in APP production could be caused by a breakdown in the blood-brain barrier during severe PTRE allowing cytokine synthesised in the brain to enter the circulation and maintain a systemic response.
在治疗后反应性脑病（PTRE）的实验模型中，研究了布氏布氏锥虫（T. b. brucei）感染小鼠期间急性期反应的刺激情况，PTRE是抗锥虫治疗的常见副作用。感染后第7天，急性期蛋白（APP）、触珠蛋白（Hp）和血清淀粉样蛋白P（SAP）的血浆水平升高，但到第20天已降至中间水平。这伴随着肝脏和大脑中细胞因子白细胞介素（IL）-6和肿瘤坏死因子-α（TNFα）的诱导。在第21天用亚治疗剂量的乙酰氨基苯脒（贝尼尔）治疗小鼠，这一过程已知会诱发轻度PTRE，寄生虫从循环中清除，血浆APP以及肝脏中IL-6和TNFα的mRNA表达恢复到对照组水平。在患有进展性PTRE的动物大脑中检测到了IL-6和TNFα的细胞因子mRNA，尽管TNFα并不比对照组显著更高。进一步给予亚治疗剂量的贝尼尔，导致更严重的PTRE，这与血清中Hp和SAP浓度升高、肝脏中TNFα mRNA增加以及大脑中可检测到的IL-6和TNFα mRNA有关。所有动物的脑和肝样本中均表达了IL-1α的mRNA。严重的PTRE引起全身性急性期反应，而轻度PTRE则不明显。两种药物治疗后细胞因子mRNA诱导模式相似。然而，APP产生的差异可能是由于严重PTRE期间血脑屏障破坏，使得大脑中合成的细胞因子进入循环并维持全身性反应所致。
