Inhibition of angiogenesis in rats by IL-1 receptor antagonist and selected cytokine antibodies.
Daily administration of 50 ng recombinant human interleukin 1-alpha (IL-1 alpha), 25 ng IL-8, 50 ng tumor necrosis factor-alpha (TNF-alpha), or 100 ng basic fibroblast growth factor (bFGF) caused intense neovascularization in a rat sponge model. These cytokine-induced neovascular responses were inhibited by coadministration of IL-1 receptor antagonist (IL-1ra; 50 micrograms), IL-8 antiserum (IL-8-AS; 1: 1000), TNF-alpha antibody (TNF-AB; 500 ng), or a monoclonal antibody to bFGF (DG2; 1000 ng), respectively. These data suggest that it is possible to manipulate the angiogenic response elicited by a defined cytokine by its receptor antagonist or neutralizing antibody. In the absence of exogenous cytokines, the sponge-induced angiogenesis was profoundly suppressed by dexamethasone (5 micrograms/day), but not modified by IL-1ra, IL-8-AS, TNF-AB, and DG2 alone. However, the combination of these four reagents was able to inhibit the sponge-induced neovascular response almost completely. These findings provide direct evidence that IL-1 alpha, IL-8, TNF-alpha and/or bFGF have an intrinsic role in angiogenesis. Further work is necessary to characterize the profile of these cytokines during angiogenesis and to elucidate the nature of their interactions.
Hu
D E
DE
Department of Pharmacology, University of Cambridge, U.K.
Hori
Y
Y
Presta
M
M
Gresham
G A
GA
Fan
T P
TP
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000906:Antibodies; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2