Reduction of eicosanoid production by essential fatty acid depletion does not attenuate the inflammatory response induced by Pseudomonas aeruginosa pneumonia in rat lung.
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)
O'Sullivan
B P
BP
Section of Pediatric Pulmonoloy, St. Christopher's Hospital for Children, Philadelphia, PA.
Mong
S
S
Votta
B
B
Schidlow
D V
DV
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015777:Eicosanoids / Q000096:biosynthesis*; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D007249:Inflammation; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D011014:Pneumonia / Q000150:complications / Q000473:pathology*; D011552:Pseudomonas Infections / Q000150:complications / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood
D004042:Dietary Fats, Unsaturated; D015777:Eicosanoids; D005228:Fatty Acids, Essential; D005231:Fatty Acids, Unsaturated; D007975:Leukotriene B4; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2