title: Endothelial structural integrity is maintained during endotoxic shock in an interleukin-1 type 1 receptor knockout mouse.
abstract: The derangement of arterial endothelial cell morphology is a good indicator of a severe shock state. Because interleukin (IL)-1 has been implicated in this process, we examined the structural integrity of aortic endothelial cells in conjunction with serum IL-6 concentrations and nitric oxide levels, which are known to increase during endotoxemia in animals genetically devoid of the type 1 IL-1 receptor. Endotoxin (10 mg/kg Escherichia coli, injected intraperitoneally) (LD100) or saline vehicle was administered to adult male C57BL/129J wild-type control mice and C57BL/129J knockout mice possessing a homozygous deletion of the type 1 IL-1 receptor. The integrity of the aortic endothelium was determined by comparisons of ultrastructure. Mice injected with sterile vehicle showed normal endothelial ultrastructure with intact membranes. Wild-type and knockout control animals receiving saline vehicle showed a complete aortic endothelium (29.11 +/- .27 and 30.85 +/- .21 intact endothelial cells per millimeter of internal elastic lamina (IEL), respectively, p = N.S.). Endotoxin-treated wild-type animals showed extensive endothelial damage with most sections showing only denuded IEL on the luminal surface (1.83 +/- .38 cells/mm IEL, p < .001 vs. control). Knockout animals treated with endotoxin showed complete maintenance of endothelial structural integrity (34.08 +/- .57 cells/mm IEL, p < .001 vs. endotoxin-treated wild type) with ultrastructural morphology appearing identical to those given saline vehicle. Also, no apparent correlation was observed between serum IL-6 concentrations or serum nitric oxide levels and aortic endothelial damage. The maintenance of endothelial integrity in animals devoid of the IL-1 receptor confirms earlier observations of endothelial cell protection with IL-1 receptor antagonism and suggests that IL-1 contributes significantly to sepsis-induced endothelial damage.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, University of South Florida, Tampa 33612, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Sutton
authors.forename: J G
authors.initials: JG
authors.lastname: Norman
authors.forename: C A
authors.initials: CA
authors.lastname: Newton
authors.forename: G R
authors.initials: GR
authors.lastname: Hellermann
authors.forename: I S
authors.initials: IS
authors.lastname: Richards
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D017472:Receptors, Interleukin-1 / Q000172:deficiency*; D053573:Receptors, Interleukin-1 Type I; D012772:Shock, Septic / Q000097:blood / Q000473:pathology*
chemical_list: D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D009569:Nitric Oxide