O'Sullivan B P, Mong S, Votta B, Schidlow D V
Section of Pediatric Pulmonoloy, St. Christopher's Hospital for Children, Philadelphia, PA.
Prostaglandins Leukot Essent Fatty Acids. 1992 Jul;46(3):203-10. doi: 10.1016/0952-3278(92)90071-p.
Sipid mediators of inflammation have been implicated in the pathogenesis of Pseudomonas aeruginosa (PA) related pulmonary damage in patients with cystic fibrosis. We studied the role of these mediators in a rat model of PA endobronchitis using essential fatty acid deficient (EFAD) animals. Whole blood from EFAD animals produced significantly less leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid when stimulated ex vivo than did whole blood from control animals (p less than 0.005). Similarly, lung lavage fluid from EFAD animals infected with PA contained less LTB4 and thromboxane B2 (TXB2) than that from control animals. Despite these differences, cellular infiltration of airways in response to PA infection was virtually identical in animals from the regular diet and the EFAD groups. Both EFAD and control animals had a significant increase in white blood cells (WBC) in lung lavage fluid at 1, 3 and 6 days following infection with PA when compared to animals receiving sterile beads. Localized areas of consolidation and nodularity were grossly evident in the lungs of all PA infected animals irrespective of their ability to generate the lipid inflammatory mediators. Microscopic examination of lung sections demonstrated similar changes in all infected animals. We conclude that LTB4 and TXB2 production occurs early in the course of PA pulmonary infection in rats. This early rise in lipid mediators is temporally associated with an influx of WBC into the airways. However, attenuation of eicosanoid production by use of an EFAD diet does not lead to a reduction in the inflammatory response to PA infection.(ABSTRACT TRUNCATED AT 250 WORDS)
炎性趋化介质被认为与囊性纤维化患者铜绿假单胞菌（PA）相关的肺损伤发病机制有关。我们使用必需脂肪酸缺乏（EFAD）的动物，在PA支气管内膜炎大鼠模型中研究了这些介质的作用。与对照动物的全血相比，EFAD动物的全血在体外受到刺激时产生的白三烯B4（LTB4）和羟基十七碳三烯酸明显更少（p<0.005）。同样，感染PA的EFAD动物的肺灌洗液中LTB4和血栓素B2（TXB2）的含量也低于对照动物。尽管存在这些差异，但正常饮食组和EFAD组动物对PA感染的气道细胞浸润实际上是相同的。与接受无菌珠子的动物相比，EFAD动物和对照动物在感染PA后1、3和6天肺灌洗液中的白细胞（WBC）均显著增加。所有感染PA的动物肺部均明显出现局部实变和结节区域，无论它们产生脂质炎症介质的能力如何。对肺切片的显微镜检查显示，所有感染动物都有类似的变化。我们得出结论，LTB4和TXB2的产生发生在大鼠PA肺部感染过程的早期。脂质介质的这种早期升高在时间上与WBC流入气道有关。然而，使用EFAD饮食减少类花生酸的产生并不会导致对PA感染的炎症反应减轻。（摘要截断于250字）
