Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Toxicol Lett. 2011 Jan 15;200(1-2):117-23. doi: 10.1016/j.toxlet.2010.11.004. Epub 2010 Nov 18.
Asthma is characterized by pulmonary cellular infiltration, vascular exudation and airway hyperresponsiveness. Several drugs that modify central nervous system (CNS) activity can modulate the course of asthma. Amphetamine (AMPH) is a highly abused drug that presents potent stimulating effects on the CNS and has been shown to induce behavioral, biochemical and immunological effects. The purpose of this study was to investigate the effects of AMPH on pulmonary cellular influx, vascular permeability and airway reactivity. AMPH effects on adhesion molecule expression, IL-10 and IL-4 release and mast cell degranulation were also studied. Male Wistar rats were sensitized with ovalbumin (OVA) plus alum via subcutaneous injection. One week later, the rats received another injection of OVA-alum (booster). Two weeks after this booster, the rats were subjected to AMPH treatment 12 h prior to the OVA airway challenge. In rats treated with AMPH, the OVA challenge reduced cell recruitment into the lung, the vascular permeability and the cellular expression of ICAM-1 and Mac-1. Additionally, elevated levels of IL-10 and IL-4 were found in samples of lung explants from allergic rats. AMPH treatment, in comparison, increased IL-10 levels but reduced those of IL-4 in the lung explants. Moreover, the tracheal responsiveness to methacholine (MCh), as well as to an in vitro OVA challenge, was reduced by AMPH treatment, and levels of PCA titers were not modified by the drug. Our findings suggest that single AMPH treatment down-regulates several parameters of lung inflammation, such as cellular migration, vascular permeability and tracheal responsiveness. These results also indicate that AMPH actions on allergic lung inflammation include endothelium-leukocyte interaction mechanisms, cytokine release and mast cell degranulation.
哮喘的特征是肺部细胞浸润、血管渗出和气道高反应性。几种能改变中枢神经系统（CNS）活动的药物可以调节哮喘的进程。安非他命（AMPH）是一种高度滥用的药物，对中枢神经系统有强烈的刺激作用，并已显示出诱导行为、生化和免疫作用的能力。本研究的目的是研究 AMPH 对肺细胞浸润、血管通透性和气道反应性的影响。还研究了 AMPH 对粘附分子表达、IL-10 和 IL-4 释放以及肥大细胞脱颗粒的影响。雄性 Wistar 大鼠通过皮下注射卵清蛋白（OVA）加明矾进行致敏。一周后，大鼠接受另一次 OVA-明矾（增强剂）注射。在接受增强剂注射两周后，大鼠在 OVA 气道挑战前 12 小时接受 AMPH 治疗。在接受 AMPH 治疗的大鼠中，OVA 挑战减少了肺内细胞募集、血管通透性和 ICAM-1 和 Mac-1 的细胞表达。此外，在过敏大鼠的肺组织样本中发现了高水平的 IL-10 和 IL-4。相比之下，AMPH 治疗增加了肺组织中 IL-10 的水平，降低了 IL-4 的水平。此外，AMPH 治疗还降低了气管对乙酰甲胆碱（MCh）和体外 OVA 挑战的反应性，并且药物不改变 PCA 滴度。我们的研究结果表明，单次 AMPH 治疗可下调肺部炎症的几个参数，如细胞迁移、血管通透性和气管反应性。这些结果还表明，AMPH 对过敏性肺部炎症的作用包括内皮细胞-白细胞相互作用机制、细胞因子释放和肥大细胞脱颗粒。
