Effect of inflammatory cytokines on human endothelial cell proliferation

✍ Scribed by Yasuhiro Saegusa; Morris Ziff; Linda Welkovich; Druie Cavender

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 925 KB
• Volume: 142
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041420307

✦ Synopsis

Neovascularization, a common occurrence in chronic inflammatory lesions, requires endothelial cell (EC) proliferation. Because this form of inflammation is often mediated by immunologically generated cytokines, the effects of such cytokines on human umbilical vein EC proliferation in vitro were investigated. Low concentrations of recombinant interferon gamma (rlFN-y) (1 0-1 00 U/ml), but not a higher concentration (1,000 Uiml), enhanced both basal and endothelial cell growth factor (ECGF)-stimulated EC proliferation. Recombinant interleukin 1 (rlL-1) and recombinant tumor necrosis factor-a (rTNF) had minor effects on basal EC proliferation, but significant inhibition was observed in the presence of ECGF. A combination of riFN-y and rTNF induced marked suppression of EC proliferation, which appeared to be due to a cytotoxic effect on the EC, as demonstrated by 5'Cr release. In contrast, the combination of rlFN-y and rlL-1 had only an additive effect on EC proliferation, with no evidence of cytotoxicity. These results suggest that cytokines have important regulatory roles in local vascular proliferation. These effects varied not only with the individual cytokine, but also with the combination of cytokines used. The most striking effects were 1) the stimulation of proliferation by IFN-y at a low concentration and 2) the inhibition by both rlL-1 and rTNF of ECGF-stimulated proliferation.