Jakab G J, Warr G A
Am Rev Respir Dis. 1981 May;123(5):524-8. doi: 10.1164/arrd.1981.123.5.524.
Pulmonary virus infections predispose to secondary bacterial pneumonias by suppressing the antibacterial defenses of the lung. Cyclophosphamide (CY) treatment interferes with antiviral defenses and also impairs pulmonary bactericidal activity. To determine whether CY aggravates secondary bacterial pneumonias, mice were infected by aerosol inhalation with para-influenza 1 (Sendai) virus and injected intraperitoneally with either 0.5, 1.0, 2.5, and 5.0 mg of CY on Days 1 and 5 of the infection. On Day 7, the lungs of control (CY-treated but not infected) and virus-infected mice were lavaged and the total and differential number of free pulmonary cells quantitated. At the same time, other groups of mice were challenged aerogenically with Staphylococcus aureus and the number of initially viable bacteria remaining in their lungs quantitated at 4 and 24 h thereafter. The CY treatment induced a dose-dependent neutropenia, which was paralleled by the number of free pulmonary cells recovered from the lungs. Pulmonary bactericidal activity was also suppressed by CY treatment, with the percentage of staphylococci remaining at 24 h in the lungs of control animals being 0.5 +/- 0.2% and 1.5 +/- 0.5%, 4.0 +/- 1.5%, 8.5 +/- 2%, and 36 +/- 5%, respectively, for the increasing doses of CY. In virus-infected animals, CY treatment suppressed the inflammatory response in a dose-dependent manner, with the total number of free lung cells recovered from the highest dose group being only 5% of that recovered from untreated animals. Virus infection depressed the antibacterial defenses of the lung so that in untreated animals, 80 +/- 9% of the staphylococcal remained at 24 h. Treatment with the 2 higher doses of CY caused the bacteria to proliferate extensively in the lungs to 280 +/- 53% and 792 +/- 112%, respectively, for the 2.5 mg and 5.0 mg CY doses. In contrast, treatment with 0.5 mg and 1.0 mg of CY significantly enhanced the intrapulmonary killing of S. aureus in virus-infected lungs so that the bactericidal values at 24 h were 28 +/- 3% and 21 +/- 2%, respectively. These data demonstrated that immunosuppression modulates virus-induced suppression of pulmonary antibacterial defenses with high doses of CY aggravating and low doses ameliorating the defect.
肺部病毒感染通过抑制肺部的抗菌防御机制，易引发继发性细菌性肺炎。环磷酰胺（CY）治疗会干扰抗病毒防御，还会损害肺部杀菌活性。为了确定CY是否会加重继发性细菌性肺炎，在感染的第1天和第5天，通过气溶胶吸入法让小鼠感染副流感1型（仙台）病毒，并分别腹腔注射0.5、1.0、2.5和5.0毫克的CY。在第7天，对对照组（接受CY治疗但未感染）和病毒感染小鼠的肺部进行灌洗，并对游离肺细胞的总数和分类数量进行定量。同时，对其他几组小鼠进行金黄色葡萄球菌气溶胶攻击，并在4小时和24小时后对其肺部中最初存活的细菌数量进行定量。CY治疗引起了剂量依赖性中性粒细胞减少，这与从肺部回收的游离肺细胞数量平行。CY治疗也抑制了肺部杀菌活性，随着CY剂量增加，对照组动物肺部24小时后残留葡萄球菌的百分比分别为0.5±0.2%、1.5±0.5%、4.0±1.5%、8.5±2%和36±5%。在病毒感染的动物中，CY治疗以剂量依赖性方式抑制炎症反应，最高剂量组回收的游离肺细胞总数仅为未治疗动物回收数量的5%。病毒感染降低了肺部的抗菌防御能力，因此在未治疗的动物中，24小时后80±9%的葡萄球菌仍存活。用2个较高剂量的CY治疗导致细菌在肺部大量增殖，2.5毫克和5.0毫克CY剂量组分别增至280±53%和792±112%。相比之下，用0.5毫克和1.0毫克的CY治疗显著增强了病毒感染肺部对金黄色葡萄球菌的肺内杀伤作用，因此24小时后的杀菌值分别为28±3%和21±2%。这些数据表明，免疫抑制调节病毒诱导的肺部抗菌防御抑制，高剂量的CY会加重缺陷，低剂量则会改善缺陷。
