AUGMENTATION OF INTERLEUKIN-1 INDUCED PROSTACYCLIN PRODUCTION BY ENDOTHELIAL-CELL GROWTH-FACTOR - IMPLICATIONS FOR CHRONIC SYNOVITIS

Interleukin-1 (IL-1) is a key inflammatory cytokine that has important effects both on endothelial cell (EC) growth and synthetic function. Fibroblast growth factors (FGFs), including endothelial cell growth fa ctor (ECGF), are important regulators of EC growth, and their role in the pannus formation and synovial proliferation seen in chronic arthri tis has been emphasized recently. While ECGF mediated EC proliferation is inhibited by IL-1, potential interaction of these peptides on othe r aspects of EC function has not been described. As both IL-1 and FGF may be important disease mediators in rheumatoid arthritis, we studied their combined effects on EC prostacyclin production. While ECGF alon e had no measurable effects, it enhanced rIL-1alpha induced prostacycl in production in a dose and time dependent fashion. Both pertussis and cholera toxins blocked the augmentation, suggesting a role for G prot eins in mediating the synergism. These studies demonstrate that ECGF c an alter certain effects of IL-1 on the endothelium, and point to an a dditional role that this family of growth factors may play in some inf lammatory disorders.