ENDOTHELIAL STRUCTURAL INTEGRITY IS MAINTAINED DURING ENDOTOXIC-SHOCKIN AN INTERLEUKIN-1 TYPE-1 RECEPTOR KNOCKOUT MOUSE

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.