ROLE OF ENDOTOXIN IN WOUND-HEALING IMPAIRMENT

We studied the effect of endotoxin on cutaneous wound healing and the mechanism involved. Rats underwent dorsal skill incision and subcutane ous placement of plastic nylon wound chambers. Immediately after this procedure, lipopolysaccharide (LPS) was administered intraperitoneally at doses of 1 to 10 mg/kg. In the rats given LPS at doses of 3 mg/kg or higher, the wound breaking strength and the production of hydroxypr oline in the wound chambers were significantly reduced in a dose-depen dent manner. The wound fluid serially collected from the wound chamber s after surgery was examined for the effect on the growth of fibroblas t. While the wound fluid from control rats showed a marked fibroblast growth-accelerating activity on postoperative day 7, this activity in the wound fluid from LPS-treated rats was significantly decreased. In the wound fluid from LPS-treated rats, the fibroblast growth-accelerat ing activity recovered to the control level by the addition of anti-TN F-alpha neutralizing antibody. These results suggested the following: wound healing is accelerated as a result of the production of fibrobla st growth factor(s) in the site of the wound. The production of tumor necrosis factor-alpha (TNF-alpha) induced by endotoxin inhibits the ef fect of the growth factor(s) in the wound area, which results in decre ased collagen production. Subsequently the wound healing process is im paired.