Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats
Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats
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DOI：
10.1046/j.1365-2249.1996.d01-618.x
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发表时间：
1996-02-01
影响因子：
4.6
通讯作者：
Hoiby, N
中科院分区：
文献类型：
--
作者：
Johansen, HK;Hougen, HP;Hoiby, N
在模拟囊性纤维化(CF)的慢性铜绿假单胞菌肺部感染的大鼠模型上，我们研究了重组大鼠干扰素-γ(rrIFM-γ)能否改变炎症反应。在大鼠气管内攻击之前或之后，将铜绿假单胞菌埋入藻酸盐微珠中进行治疗。与攻击前(P=0.004)和对照组(P=0.003)相比，攻击后处理组大鼠的肉眼肺部炎症严重程度显著减轻。对照组的组织病理学以大量多形核白细胞(PMN)(大于或等于90%)围绕着藻酸盐小球为主，如在CF中。这可能是由类Th2反应引起的。相反，在两组大鼠中都观察到完全转变为以单核白细胞(大于或等于90%的淋巴细胞和浆细胞)和肉芽肿为主的慢性型炎症。这可能是由类Th1反应引起的。两组之间的致死率没有显著差异，治疗组和对照组大鼠对铜绿假单胞菌超声波和藻酸盐的抗体效价相似。由于持续的肺组织损伤是由PMN分泌的弹性蛋白酶引起的，PMN是铜绿假单胞菌肺部感染的主导因素，我们的发现为改善CF患者的炎症反应提供了一种可能的新策略。
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(rrIFM-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) (greater than or equal to 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 (greater than or equal to 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.