TUMOR-NECROSIS-FACTOR-ALPHA (RHTNF) FAILS TO STIMULATE ANGIOGENESIS IN THE RABBIT CORNEA

Background: The objective of this study was to thoroughly examine the in vivo angiogenesis activity of human recombinant tumor necrosis fact or alpha (rhTNF). Methods: rhTNF (0.5 ng to 1.0 mu g) was incorporated into the slow release polymers Hydron or HYPAN (R) and implanted into the rabbit cornea. Release of biologically active rhTNF from the poly mers was determined with the L929 cytotoxicity assay. Results: All con centrations tested failed to elicit capillary formation beyond that ob served for controls. Less than 2% of the rhTNF was released from the H ydron over 7 days. HYPAN (R) released five times the amount of rhTNF i n vitro, but even at doses of 500 ng (104.3 ng suggested release) no a ngiogenesis was stimulated. Conclusion: Under the circumstances tested , rhTNF is not angiogenic in vivo. (C) 1996 Wiley-Liss, Inc.