Inhibition of angiogenesis by interleukin 4

• Published in: The Journal of experimental medicine Vol. 188; no. 6; pp. 1039 - 1046
• Main Authors: Volpert, O V, Fong, T, Koch, A E, Peterson, J D, Waltenbaugh, C, Tepper, R I, Bouck, N P
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 21.09.1998
• Subjects: Adenocarcinoma; Animals; Cell Movement - drug effects; Cell Movement - immunology; Cells, Cultured; Cornea - blood supply; Cornea - drug effects; Cornea - immunology; Culture Media, Conditioned - chemistry; Culture Media, Serum-Free - chemistry; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - immunology; Humans; Immunosuppressive Agents - pharmacology; Injections, Intraperitoneal; Interleukin-4 - administration & dosage; Interleukin-4 - physiology; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - immunology; Rats; Tumor Cells, Cultured
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.188.6.1039

Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose-response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (TH0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.