Sato K, Suga M, Akaike T, Fujii S, Muranaka H, Doi T, Maeda H, Ando M
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):853-7. doi: 10.1164/ajrccm.157.3.9703098.
Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.
红霉素（EM）是一种具有强大抗炎作用的抗生素，用于治疗慢性下呼吸道感染。研究表明，超氧阴离子和一氧化氮（NO）等自由基是病毒性疾病中的致病分子。NO在各种炎症性疾病的病理过程中的关键作用已受到广泛关注。在本研究中，我们评估了EM对感染致死剂量甲型流感病毒A/熊本/Y5/67（H2N2）的小鼠流感病毒诱导性肺炎的影响。以3.3mg/kg/d的剂量（腹腔注射，感染后第1天至第6天）给予EM，显著提高了感染流感病毒小鼠的存活率，并且在感染后第20天，病毒感染小鼠的存活率随着给予动物的EM剂量增加而呈剂量依赖性增加，从对照组的14%增加到给予1.0mg/kg/d EM的动物组的42%，以及给予3.3mg/kg/d EM的动物组的57%。感染后第6天，EM治疗抑制了小鼠肺中γ干扰素（IFN-γ）的诱导。同时，EM治疗显著减少了病毒感染6天后肺灌洗液中回收的炎症细胞数量。EM治疗导致病毒感染小鼠血清中亚硝酸盐/硝酸盐（NO的代谢产物）水平呈剂量依赖性降低，以及肺中一氧化氮合酶（NOS）诱导潜力降低。这些结果表明，EM可能通过抑制炎症细胞反应和抑制肺中NO的过度产生，对流感病毒诱导性肺炎等各种急性炎症性疾病具有重要的治疗价值。
