Et. Sutton et al., ENDOTHELIAL STRUCTURAL INTEGRITY IS MAINTAINED DURING ENDOTOXIC-SHOCKIN AN INTERLEUKIN-1 TYPE-1 RECEPTOR KNOCKOUT MOUSE, Shock, 7(2), 1997, pp. 105-110
The derangement of arterial endothelial cell morphology is a good indi
cator of a severe shock state. Because interleukin (IL)-1 has been imp
licated in this process, we examined the structural integrity of aorti
c 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 sali
ne 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 steri
le Vehicle showed normal endothelial ultrastructure with intact membra
nes. Wild-type and knockout control animals receiving saline vehicle s
howed a complete aortic endothelium (29.11+/-.27 and 30.85+/-.21 intac
t endothelial cells per millimeter of internal elastic lamina (IEL), r
espectively, p=N.S.). Endotoxin-treated wild-type animals showed exten
sive endothelial damage with most sections showing only denuded IEL on
the luminal surface (1.83+/-.38 cells/mm IEL, p <.001 vs. control). K
nockout 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 appeari
ng identical to those given saline vehicle. Also, no apparent correlat
ion was observed between serum IL-6 concentrations or serum nitric oxi
de levels and aortic endothelial damage. The maintenance of endothelia
l integrity in animals devoid of the IL-1 receptor confirms earlier ob
servations of endothelial cell protection with IL-1 receptor antagonis
m and suggests that IL-1 contributes significantly to sepsis-induced e
ndothelial damage.