Endothelial structural integrity is maintained during endotoxic shock in an interleukin-1 type 1 receptor knockout mouse

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) (LD(100)) 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.