Tumor necrosis factor binding protein improves incisional wound healing in sepsis

Sepsis is associated with poor wound healing; however, the exact role of tumor necrosis factor (TNF) as a mediator of sepsis-induced 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.

Three groups of male Sprague-Dawley rats were studied: control, sepsis, and sepsis + 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 prior 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 sponges was used to quantitate collagen content under the different experimental conditions.

Septic mortality (20% vs 26%) was not significantly altered by TNFbp. Septic animals demonstrated a reduction in food consumption on days 3 to 5 that was not affected by TNFbp administration. Neither sepsis nor TNFbp altered the breaking strength or histologic 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 significantly improved incisional WBS (P < 0.01 vs sepsis), but not to control levels. Serius red staining of incisional wounds and PVA sponges demonstrated a decrease in collagen organization and deposition in septic rats that was ameliorated by TNFbp. Similarly, the reduction in hydroxyproline content of PVA sponges from septic animals was prevented by TNFbp.

The process of tissue repair in intestine and skin wounds appears to be significantly different following the septic insult. The healing of jejunal anastomoses was refractory to the catabolic effects of sepsis. In contrast, collagen deposition and organization are significantly decreased in cutaneous wounds during chronic sepsis. TNFbp significantly ameliorated the inhibitory effects of sepsis on cutaneous wound healing. These results suggest that TNF is an important mediator of the decrease in collagen deposition observed in cutaneous wounds during the septic state.