Ligeiro-Oliveira A P, Fialho de Araújo A M, Lazzarini R, Silva Z L, De Nucci G, Muscará M N, Tavares de Lima W, Palermo-Neto J
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Neuroimmunomodulation. 2004;11(3):181-90. doi: 10.1159/000076767.
The present study analyzed the effects of acute amphetamine (AMPH) treatment on immune-mediated lung inflammatory response in rats.
There were four experiments. In the first and second experiments, rats were treated with AMPH (1 mg/kg) or 0.9% NaCl, and locomotor activity (experiment 1) and serum AMPH concentrations (experiment 2) were measured 1 or 12 h after treatment. In the third experiment, rats which were immunized with ovalbumin (OVA) were treated 14 days later with 0.9% NaCl or AMPH (1 mg/kg). Twelve hours after these treatments, all animals were submitted to challenge by 1% OVA inhalation being analyzed afterwards for bronchoalveolar lavage fluid (BAL), peripheral blood and bone marrow cellularity. In the fourth and final experiment, rats were treated and studied as for experiment 3, except that half of the animals within each group were previously treated with metyrapone prior to the OVA challenge.
In the non-immunized rats, AMPH treatment induced an increase in locomotor activity synchronized to high serum AMPH concentrations 1 h after, but not 12 h after treatment. In OVA-challenged rats, AMPH treatment decreased the total number of inflammatory cells, recovered in both BAL and peripheral blood and increased the total number of bone marrow cells. These effects, observed 1 day after OVA challenge, were abrogated by previous metyrapone treatment.
AMPH treatment changed HPA-axis responsiveness to the stress condition imposed by the OVA challenge decreasing lung and blood leukocytes cellularity most probably via corticosterone actions on bone marrow activity.
本研究分析了急性苯丙胺(AMPH)处理对大鼠免疫介导的肺部炎症反应的影响。
共有四项实验。在第一项和第二项实验中,给大鼠注射AMPH(1毫克/千克)或0.9%氯化钠,在处理后1小时或12小时测量其运动活性(实验1)和血清AMPH浓度(实验2)。在第三项实验中,用卵清蛋白(OVA)免疫的大鼠在14天后接受0.9%氯化钠或AMPH(1毫克/千克)处理。这些处理12小时后,所有动物通过吸入1%OVA进行激发,随后对支气管肺泡灌洗液(BAL)、外周血和骨髓细胞进行分析。在第四项也是最后一项实验中,大鼠的处理和研究方式与实验3相同,只是每组中有一半动物在OVA激发前预先用甲吡酮处理。
在未免疫的大鼠中,AMPH处理导致处理后1小时而非12小时运动活性增加,且与高血清AMPH浓度同步。在OVA激发的大鼠中,AMPH处理减少了在BAL和外周血中回收的炎症细胞总数,并增加了骨髓细胞总数。在OVA激发后1天观察到的这些效应,被预先的甲吡酮处理消除。
AMPH处理改变了HPA轴对OVA激发所施加应激条件的反应性,最有可能通过皮质酮对骨髓活性的作用降低肺和血液中的白细胞细胞数。