Inhibition by IL-1 of endothelial cell activation induced by tumor necrosis factor or lymphotoxin.
Previous studies in this and other laboratories have demonstrated that IL-1, lymphotoxin (LT), and TNF rapidly stimulate a number of proinflammatory properties in cultured endothelial cells (EC) including cell-surface procoagulant activity and increased adhesivity for lymphocytes, monocytes, and polymorphonuclear leukocytes. In addition, we have demonstrated that LT and TNF, but not IL-1, stimulate increases in EC RNA synthesis, protein synthesis, and cellular volumes, changes which may correspond to the hypertrophy of EC seen at sites of inflammation in vivo. It is reported here that both human rIL-1 alpha and rIL-1 beta totally inhibit the increases in EC RNA synthesis, protein synthesis, and cell volumes induced by either TNF or LT. As little as 0.1 ng/ml of either IL-1 was sufficient to totally block the activation of EC induced by 100-fold higher concentrations (10 ng/ml) of either LT or TNF. The relevance of these findings to the regulation of inflammatory responses is discussed.
Cavender
D E
DE
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9030.
Edelbaum
D
D
D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D012313:RNA