Pennington J E, Hickey W F, Blackwood L L, Arnaut M A
J Clin Invest. 1981 Nov;68(5):1140-8. doi: 10.1172/jci110358.
Chronic respiratory infection with Pseudomonas aeruginosa is a leading clinical problem among patients with cystic fibrosis. Because antimicrobial agents are usually ineffective in eradicating these infections, additional therapeutic or prophylactic measures should be considered. In this study, an experimental guinea pig model of chronic Pseudomonas aeruginosa bronchopneumonia was utilized to determine whether active immunization with lipopolysaccharide (LPS) P. aeruginosa antigen may favorably influence the course of this infection. Experimental pneumonia was established by tracheobronchial instillation of suspensions of microscopic agar beads, which were impregnated with viable P. aeruginosa. After 4 wk of infection, the geometric mean (reciprocal) passive hemagglutinating Pseudomonas antibody titer was 185+/-1.3, and lungs contained 16.8+/-4 x 10(3) colony-forming units Pseudomonas/ml of lung homogenate. Pseudomonas immunization, given prior to a 4-wk infection, resulted in significantly higher passive hemagglutinating titers (474+/-1.4; P < 0.05), lower numbers of viable Pseudomonas in lung tissues (2.4+/-0.6 x 10(3); P < 0.01), and reduced histopathology in lungs. In contrast, providing Pseudomonas immunization to animals 2 wk after pulmonary infection was established, offered no apparent benefit. Likewise, no protection was afforded by prophylactic immunization with a non-Pseudomonas LPS antigen (Escherichia coli J5 vaccine). Using a Raji cell assay, modified to detect circulating immune complexes in vaccinated and infected guinea pig sera, there was no evidence that active immunization increased the frequency of circulating immune complexes in infected guinea pigs. It is concluded that prophylactic immunization with Pseudomonas LPS antigen may confer protection from subsequent Pseudomonas bronchopneumonia, but that immunization during established infection is not beneficial.
铜绿假单胞菌慢性呼吸道感染是囊性纤维化患者面临的主要临床问题。由于抗菌药物通常无法有效根除这些感染,因此应考虑采取额外的治疗或预防措施。在本研究中,利用慢性铜绿假单胞菌支气管肺炎的实验性豚鼠模型,来确定用铜绿假单胞菌脂多糖(LPS)抗原进行主动免疫是否会对该感染病程产生有利影响。通过气管支气管内滴注含有活铜绿假单胞菌的微小琼脂珠悬液来建立实验性肺炎。感染4周后,被动血凝铜绿假单胞菌抗体滴度的几何平均值(倒数)为185±1.3,肺组织中每毫升肺匀浆含有16.8±4×10³ 个铜绿假单胞菌集落形成单位。在4周感染前进行铜绿假单胞菌免疫,可使被动血凝滴度显著升高(474±1.4;P<0.05),肺组织中活铜绿假单胞菌数量减少(2.4±0.6×10³;P<0.01),且肺部组织病理学变化减轻。相比之下,在肺部感染建立2周后对动物进行铜绿假单胞菌免疫,未显示出明显益处。同样,用非铜绿假单胞菌LPS抗原(大肠杆菌J5疫苗)进行预防性免疫也未提供保护作用。使用经改良以检测接种疫苗和感染豚鼠血清中循环免疫复合物的Raji细胞试验,没有证据表明主动免疫会增加感染豚鼠循环免疫复合物的频率。结论是,用铜绿假单胞菌LPS抗原进行预防性免疫可能对后续铜绿假单胞菌支气管肺炎起到保护作用,但在已建立感染期间进行免疫并无益处。