Maris Nico A, Florquin Sandrine, van't Veer Cornelis, de Vos Alex F, Buurman Wim, Jansen Henk M, van der Poll Tom
Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Respir Res. 2006 Apr 4;7(1):57. doi: 10.1186/1465-9921-7-57.
Nontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease. Inhalation of beta2-receptor agonists is a widely used treatment in patients with chronic obstructive pulmonary disease. The aim of this study was to determine the effect of inhalation of beta2 agonists on the host immune response to respiratory tract infection with NTHi.
Mouse alveolar macrophages were stimulated in vitro with NTHi in the presence or absence of the beta2 receptor agonists salmeterol or salbutamol. In addition, mice received salmeterol or salbutamol by inhalation and were intranasally infected with NTHi. End points were pulmonary inflammation and bacterial loads.
Both salmeterol and salbutamol inhibited NTHi induced tumor necrosis factor-alpha (TNFalpha) release by mouse alveolar macrophages in vitro by a beta receptor dependent mechanism. In line, inhalation of either salmeterol or salbutamol was associated with a reduced early TNFalpha production in lungs of mice infected intranasally with NTHi, an effect that was reversed by concurrent treatment with the beta blocker propranolol. The clearance of NTHi from the lungs was impaired in mice treated with salmeterol or salbutamol, an adverse effect that was prevented by propranolol and independent of the reduction in TNFalpha.
These data suggest that inhalation of salmeterol or salbutamol may negatively influence an effective clearance of NTHi from the airways.
不可分型流感嗜血杆菌（NTHi）是一种常见的细菌病原体，在诸如慢性阻塞性肺疾病等允许条件下可引起人类呼吸道感染。吸入β2受体激动剂是慢性阻塞性肺疾病患者广泛使用的一种治疗方法。本研究的目的是确定吸入β2激动剂对宿主针对NTHi呼吸道感染的免疫反应的影响。
在有或没有β2受体激动剂沙美特罗或沙丁胺醇存在的情况下，用NTHi体外刺激小鼠肺泡巨噬细胞。此外，小鼠通过吸入接受沙美特罗或沙丁胺醇，并经鼻感染NTHi。终点指标为肺部炎症和细菌载量。
沙美特罗和沙丁胺醇在体外均通过β受体依赖性机制抑制NTHi诱导的小鼠肺泡巨噬细胞释放肿瘤坏死因子-α（TNFα）。同样，吸入沙美特罗或沙丁胺醇与经鼻感染NTHi的小鼠肺部早期TNFα产生减少有关，β受体阻滞剂普萘洛尔同时治疗可逆转这一效应。用沙美特罗或沙丁胺醇治疗的小鼠肺部NTHi的清除受损，普萘洛尔可预防这一不良效应，且该效应与TNFα的减少无关。
这些数据表明，吸入沙美特罗或沙丁胺醇可能对从气道有效清除NTHi产生负面影响。
