Role of endotoxin in wound healing impairment.

We studied the effect of endotoxin on cutaneous wound healing and the mechanism involved. Rats underwent dorsal skin incision and subcutaneous 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 hydroxyproline in the wound chambers were significantly reduced in a dose-dependent manner. The wound fluid serially collected from the wound chambers after surgery was examined for the effect on the growth of fibroblast. 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-accelerating activity recovered to the control level by the addition of anti-TNF-alpha neutralizing antibody. These results suggested the following: wound healing is accelerated as a result of the production of fibroblast growth factor(s) in the site of the wound. The production of tumor necrosis factor-alpha (TNF-alpha) induced by endotoxin inhibits the effect of the growth factor(s) in the wound area, which results in decreased collagen production. Subsequently the wound healing process is impaired.