Tumor necrosis factor mediates impaired wound healing in chronic abdominal sepsis

Background: The role of systemic tumor necrosis factor (TNF) as a mediator of impaired wound healing in sepsis is unclear. The purpose of this study was to examine the effects of a specific TNF antagonist (TNFbp) on wound healing during chronic abdominal sepsis. Methods: Male Sprague-Dawley rats were divided into four groups: control, control+TNFbp, sepsis, and sepsis+TNFbp. Saline (1.0 mL) or TNFbp (1 mg/kg, 1.0 mL) was injected subcutaneously daily, polyvinylalcohol (PVA) sponge implants were placed in subcutaneous pockets, and sepsis was induced by creation of a chronic, intra- abdominal abscess. Sponge implants were removed on day 5 and examined histologically. Granulation tissue infiltration and quality (connective tissue, cellularity, vascularity) were scored on a scale from 1 to 4 in a blinded fashion. Results: Septic mortality (19 vs. 25%) was not influenced by TNFbp. Granulation tissue penetration and quality were decreased in septic animals. The administration of TNFbp significantly attenuated the effects of sepsis on granulation tissue histology, but not to control levels. Conclusions: These studies provide evidence that TNF contributes to the impaired wound healing observed in this model of chronic abdominal sepsis.