Castro Shawn Monique, Guerrero-Plata Antonieta, Suarez-Real Giovanni, Adegboyega Patrick A, Colasurdo Giuseppe N, Khan Amir M, Garofalo Roberto P, Casola Antonella
Department of Pediatrics, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-0366, USA.
Am J Respir Crit Care Med. 2006 Dec 15;174(12):1361-9. doi: 10.1164/rccm.200603-319OC. Epub 2006 Sep 28.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in children. No treatment has been shown to significantly improve the clinical outcome of patients with this infection. Recent evidence suggests that oxidative stress could play an important role in the pathogenesis of acute and chronic lung inflammatory diseases. We do not known whether RSV induces pulmonary oxidative stress and whether antioxidant treatment can modulate RSV-induced lung disease.
To investigate the effect of antioxidant administration on RSV-induced lung inflammation, clinical disease, and airway hyperreactivity (AHR).
BALB/c mice were infected with 10(7) plaque-forming units of RSV, in the presence or absence of orally administered butylated hydroxyanisole (BHA), an antioxidant. Malondialdehyde and 4-hydroxynonenal were measured in bronchoalveoar lavage (BAL) by colorimetric assay. Cytokines and chemokines were measured in BAL by Bio-Plex and leukotrienes were measured by enzyme-linked immunosorbent assay. AHR to methacholine challenge was measured by whole-body plethysmography.
BHA treatment significantly attenuated RSV-induced lung oxidative stress, as indicated by the decrease of malondialdehyde and 4-hydroxynonenal content in BAL of RSV-infected mice. RSV-induced clinical illness and body weight loss were also reduced by BHA treatment, which inhibited neutrophil recruitment to the lung and significantly reduced pulmonary cytokine and chemokine production after RSV infection. Similarly, antioxidant treatment attenuated RSV-induced AHR.
Modulation of oxidative stress represents a potential novel pharmacologic approach to ameliorate RSV-induced acute lung inflammation and potentially prevent long-term consequences associated with RSV infection, such as bronchial asthma.
呼吸道合胞病毒（RSV）是儿童下呼吸道感染的主要病因。尚无治疗方法显示能显著改善该感染患者的临床结局。近期证据表明，氧化应激可能在急性和慢性肺部炎症性疾病的发病机制中起重要作用。我们尚不清楚RSV是否会诱导肺部氧化应激，以及抗氧化治疗能否调节RSV诱发的肺部疾病。
研究抗氧化剂给药对RSV诱发的肺部炎症、临床疾病及气道高反应性（AHR）的影响。
在有或无口服抗氧化剂丁基羟基茴香醚（BHA）的情况下，用10⁷ 蚀斑形成单位的RSV感染BALB/c小鼠。通过比色法测定支气管肺泡灌洗（BAL）中的丙二醛和4-羟基壬烯醛。通过Bio-Plex测定BAL中的细胞因子和趋化因子，通过酶联免疫吸附测定法测定白三烯。通过全身体积描记法测定对乙酰甲胆碱激发的气道高反应性。
BHA治疗显著减轻了RSV诱导的肺部氧化应激，RSV感染小鼠BAL中丙二醛和4-羟基壬烯醛含量的降低表明了这一点。BHA治疗还减轻了RSV诱发的临床疾病和体重减轻，抑制了中性粒细胞向肺部的募集，并显著降低了RSV感染后肺部细胞因子和趋化因子的产生。同样，抗氧化剂治疗减轻了RSV诱导的气道高反应性。
调节氧化应激代表了一种潜在的新型药理学方法，可改善RSV诱发的急性肺部炎症，并可能预防与RSV感染相关的长期后果，如支气管哮喘。
