title: Immunopathogenesis of atherosclerosis: endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet.
abstract: BACKGROUND
  On the basis of our concept that atherosclerosis has an immunopathological background, we tested whether activation of the innate immune system influences its progression.
  
  
  RESULTS
  Hypercholesterolemic (0.5% wt/wt diet) rabbits received either repeated intravenous injections of endotoxin (Escherichia coli lipopolysaccharide 1.25 to 2.5 microg, once per week) or a self-limiting cutaneous Staphylococcus aureus infection with or without a quinolone antibiotic. Measured laboratory parameters, including LDL and HDL cholesterols, were similar in the different groups of hypercholesterolemic animals. All endotoxin-treated animals developed transient episodes of fever after endotoxin administration. The extent of atherosclerosis was evaluated by computer-assisted morphometry in the aortas en face (Sudan IV) and by histology at 8 weeks after start of the experiments. Endotoxin-treated animals exhibited significantly accelerated atherosclerosis compared with control animals (141+/-38 versus 45+/-16 mm(3) total lesion volume, n=7 to 9 rabbits each, P<0.001).
  
  
  CONCLUSIONS
  Nonspecific stimulation of the innate immune system accelerates cholesterol-induced atherosclerosis. These data support the concept that atherosclerosis has an immunopathological component and render it improbable that a single infectious agent should assume particular importance in its initiation or progression.
authors.affiliation: Institute of Pathology, University of Mainz, Germany.
authors.forename: H A
authors.initials: HA
authors.lastname: Lehr
authors.forename: T A
authors.initials: TA
authors.lastname: Sagban
authors.forename: C
authors.initials: C
authors.lastname: Ihling
authors.forename: U
authors.initials: U
authors.lastname: Zähringer
authors.forename: K D
authors.initials: KD
authors.lastname: Hungerer
authors.forename: M
authors.initials: M
authors.lastname: Blumrich
authors.forename: K
authors.initials: K
authors.lastname: Reifenberg
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D018450:Disease Progression; D004731:Endotoxins / Q000276:immunology / Q000633:toxicity*; D005260:Female; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D007113:Immunity, Innate / Q000276:immunology*; D011817:Rabbits; D013207:Staphylococcal Skin Infections / Q000276:immunology; D014280:Triglycerides / Q000097:blood
chemical_list: D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004731:Endotoxins; D014280:Triglycerides; D002784:Cholesterol