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Vacuum Assisted Closure (V.A.C.) Therapy has previously been shown to facilitate healing of wounds. However, the physiological mechanism(s) of this treatment modality and its systemic effects require further investigations. The goal of this porcine study was to investigate the effect of V.A.C. Therapy on the systemic distribution of the inflammatory cytokines interleukin (IL)-6, IL-8, IL-10, and transforming growth factor-beta1. Twelve pigs were each given one full-thickness excisional wound, using electrocautery. Six of the pigs were treated with V.A.C. Therapy and six with saline-moistened gauze. Serum samples were collected immediately after wound creation, and hourly for 4 hours. Samples were analyzed using commercially available enzyme-linked immunosorbent assay kits. During the initial 4 hours of treatment, V.A.C. Therapy resulted in earlier and greater peaking of IL-10 and maintenance of IL-6 levels compared with saline-moistened gauze controls, which showed decreased IL-6 values over the first hour (both at p<0.05). No other treatment-based differences were detected.