TUMOR-NECROSIS-FACTOR BINDING-PROTEIN IMPROVES INCISIONAL WOUND-HEALING IN SEPSIS

Background. Sepsis is associated with poor wound healing; however, the exact role of tumor necrosis factor (TNF) as a mediator of sepsis-ind uced alterations in different types of tissue repair is unknown. This study examines the effects of a specific TNF antagonist (TNFbp) on the healing of intestinal anastomoses, incisional wounds, and polyvinyl ( PVA) sponge implants in chronic abdominal sepsis. Methods. Three group s of male Sprague-Dawley rats were studied: control, sepsis, and sepsi s + TNFbp. Jejunal resection and anastomosis were performed through a 4-cm upper midline incision on day 1. On day 3, sepsis was induced by creation of a chronic abdominal abscess. Saline (0.1 ml) or TNFbp (1.0 mg/kg, 0.1 ml) was injected subcutaneously every day starting 4 h pri or to sepsis. On day 7, the wound-breaking strength (WBS) of the skin incision and intestinal anastomoses was determined using a tensiometer . Wound histology and collagen deposition were evaluated by comparison of Sirius red-stained sections. The hydroxyproline content of PVA spo nges was used to quantitate collagen content under the different exper imental conditions. Results. Septic mortality (20% vs 26%) was not sig nificantly altered by TNFbp. Septic animals demonstrated a reduction i n food consumption on days 3 to 5 that was not affected by TNFbp admin istration. Neither sepsis nor TNFbp altered the breaking strength or h istologic appearance of intestinal anastomoses. However, the breaking strength of incisional wounds was decreased by 40% in septic rats (P < 0.001 vs controls). Administration of TNFbp to septic rats significan tly improved incisional WBS (P < 0.01 vs sepsis), but not to control l evels. Serius red staining of incisional wounds and PVA sponges demons trated a decrease in collagen organization and deposition in septic ra ts that was ameliorated by TNFbp. Similarly, the reduction in hydroxyp roline content of PVA sponges from septic animals was prevented by TNF bp. Conclusions. The process of tissue repair in intestine and skin wo unds appears to be significantly different following the septic insult . The healing of jejunal anastomoses was refractory to the catabolic e ffects of sepsis. In contrast, collagen deposition and organization ar e significantly decreased in cutaneous wounds during chronic sepsis. T NFbp significantly ameliorated the inhibitory effects of sepsis on cut aneous wound healing. These results suggest that TNF is an important m ediator of the decrease in collagen deposition observed in cutaneous w ounds during the septic state. (C) 1998 Academic Press.