Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability.
Endotoxic shock is associated with acute vascular endothelial injury resulting in edema. Tumor necrosis factor (TNF) and interleukin 1 (IL-1) are cytokines produced by endotoxin-stimulated mononuclear phagocytes that are potential mediators of endotoxic shock. In this study, we investigated the effects of TNF and IL-1 alpha on vascular endothelial cell permeability in vitro. The movement of radiolabeled macromolecules of different sizes (57Co-vitamin B12, 125I-cytochrome c, and 131I-albumin; 6.5-35A) across bovine aortic endothelial cell monolayers was measured after exposure to these cytokines. TNF induced a time- and dose-dependent increase in endothelial cell monolayer permeability that was enhanced in the presence of serum. The peak increase was noted after 12 h of incubation with less alteration of permeability with longer incubations. IL-1 alpha caused a similar time-dependent increase in endothelial cell monolayer permeability, but the peak effect of IL-1 alpha was seen after 24 h. Therefore the increased permeability seen with TNF cannot be explained by release of endogenous IL-1 alone. Neither TNF nor IL-1 alpha increased release of [14C]adenine, and the only effect on lactate dehydrogenase release was a small, but statistically significant, increase after 24 h of incubation. From these studies, we conclude that TNF and IL-1 alpha directly increase vascular endothelial cell permeability in vitro and speculate that these cytokines may be involved in the acute vascular endothelial injury associated with endotoxic shock.
Royall
J A
JA
Department of Pediatrics, University of Alabama, Birmingham 35294.
Berkow
R L
RL
Beckman
J S
JS
Cunningham
M K
MK
Matalon
S
S
Freeman
B A
BA
D000225:Adenine / Q000378:metabolism; D000818:Animals; D001011:Aorta; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008433:Mathematics; D008954:Models, Biological; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D000225:Adenine