DELAYED WOUND-HEALING AND DISORGANIZED NEOVASCULARIZATION IN TRANSGENIC MICE EXPRESSING THE IP-10 CHEMOKINE

IP-10 is a member of the or or cysteine-X amino acid-cysteine (CXC) ch emokine family of chemotactic cytokines. High levels of IP-10 expressi on have been detected in a number of chronic human inflammatory condit ions, including psoriasis, a common inflammatory disease of the skin. IP-10 has been shown to chemoattract activated T cells, inhibit the pr oliferation of endothelial cells, and inhibit the growth of tumors in vivo. To determine the capacity of IP-10 to modulate the inflammatory response in vivo, we have created transgenic mice that constitutively express IP-10 from keratinocytes. These mice developed normally and, i n general, did not spontaneously recruit leukocytes into the skin or o ther organs that expressed the transgene. In addition, the transgenic mice had a normal cutaneous contact hypersensitivity cellular immune r esponse. However, IP-10 transgenic mice had an abnormal wound healing response characterized by a more intense inflammatory phase and a prol onged and disorganized granulation phase with impaired blood vessel fo rmation. These results have demonstrated that IP-10 can inhibit the ne ovascularization associated with a physiological response in vivo and have revealed a novel biologic activity of IP-10 as an inhibitor of wo und healing.