Johansen H K, Hougen H P, Rygaard J, Høiby N
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Clin Exp Immunol. 1996 Feb;103(2):212-8. doi: 10.1046/j.1365-2249.1996.d01-618.x.
In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal challenge with P. aeruginosa embedded in alginate beads. Rats treated after challenge had a significant reduction in the severity of macroscopic lung inflammation compared with rats treated before challenge (P = 0.004) and controls (P = 0.003). The histopathology in controls was dominated by numerous polymorphonuclear leucocytes (PMN) (> or = 90%) surrounding the alginate beads like in CF. This could be caused by a Th2-like response. In contrast, a complete shift to a chronic-type inflammation dominated by mononuclear leucocytes (> or = 90% lymphocytes and plasma cells) and granulomas was observed in both rrIFN-gamma-treated groups of rats. This could be caused by a Th1-like response. There was no significant difference in lethality between the groups, and the antibody titres against P. aeruginosa sonicate and alginate were similar in the treated rats and controls. Since the ongoing lung tissue damage in CF patients has been shown to be caused by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our findings offer a possible new strategy of modifying the inflammatory response in CF patients.
在一种模拟囊性纤维化（CF）的慢性铜绿假单胞菌肺部感染大鼠模型中，我们研究了腹腔注射重组大鼠干扰素-γ（rrIFN-γ）是否能改变炎症反应。大鼠在经气管内注射包埋于藻酸盐珠中的铜绿假单胞菌之前或之后接受治疗。与攻击前治疗的大鼠（P = 0.004）和对照组（P = 0.003）相比，攻击后治疗的大鼠肺部宏观炎症的严重程度显著降低。对照组的组织病理学表现为藻酸盐珠周围有大量多形核白细胞（PMN）（≥90%），如同在CF中所见。这可能是由类似Th2的反应引起的。相反，在两组接受rrIFN-γ治疗的大鼠中均观察到完全转变为以单核白细胞（≥90%淋巴细胞和浆细胞）和肉芽肿为主的慢性炎症类型。这可能是由类似Th1的反应引起的。各组之间的致死率无显著差异，治疗大鼠和对照组中针对铜绿假单胞菌超声裂解物和藻酸盐的抗体滴度相似。由于CF患者持续的肺组织损伤已被证明是由PMN分泌的弹性蛋白酶引起的，PMN在铜绿假单胞菌肺部感染中占主导地位，我们的研究结果为改变CF患者炎症反应提供了一种可能的新策略。
