title: Inflammatory responses to neutral fat and fatty acids in multiple organs in a rat model of fat embolism syndrome.
abstract: Fat embolism syndrome (FES) is a common complication of long bone fractures. FES is rare but with significant morbidity and occasional fatalities. Studies of animal models of FES are numerous; however, few studies compare inflammatory reactions in multiple organs. The present study investigated the effect of neutral fat and fatty acids, which cause changes in multiple organs and induce FES. Using rats we evaluated the ratio of lung-to-body weight and conducted histological analyses and quantitative analysis of inflammatory cytokine mRNAs in the lungs following intravenous administration of neutral fat or fatty acids. Neutral fat increased the ratio of lung-to-body weight, and neutral fat formed emboli in lung capillaries. The levels of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in the lungs increased after injection of neutral fat and oleic acid. Analysis of the histologic changes revealed that the highest numbers of fat droplets, occluding the capillaries of the lungs, kidney, heart, and brain formed 12h after the injection of neutral fat and fat droplets gradually diminished 48h later. Fat droplets were not detected in any organs after the injection of oleic acid. IL-1β and TNF-α levels in the lungs were elevated 9-24h after the injection of neutral fat, although IL-6 levels peaked at 6h. After injection of oleic acid, peak levels of IL-1β, IL-6, and TNF-α were detected at 6h, and IL-6 again increased in all organs and plasma at 15h. Neutral fat, but not fatty acids, formed emboli in the capillaries of multiple organs. These findings suggest that neutral fat increased inflammatory cytokine levels by forming emboli in organ capillaries, particularly in the lungs, while oleic acid augmented inflammatory cytokine levels by stimulating endothelial cells of multiple organs.
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: m2takada@marianna-u.ac.jp.
authors.forename: Meri
authors.initials: M
authors.lastname: Takada
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Shoetsu
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshita
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ikawa
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Morihisa
authors.initials: M
authors.lastname: Sagi
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Ichiba
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Toshiji
authors.initials: T
authors.lastname: Mukai
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004620:Embolism, Fat / Q000473:pathology*; D005227:Fatty Acids / Q000008:administration & dosage*; D049429:Forensic Pathology; D007267:Injections; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D050151:Subcutaneous Fat / Q000637:transplantation*
chemical_list: D016207:Cytokines; D005227:Fatty Acids; D012333:RNA, Messenger
keywords: Fat embolism syndrome; Fatty acid; Inflammatory cytokine; Neutral fat; Rat