The proposed investigation is a randomized, double-blind, placebo and positive-controlled within-subjects design clinical study to evaluate the role of the cytokine tumor necrosis factor (TNF) in acute inflammation using a specific TNF receptor antagonist, etanercept (Enbrel, Immunex Corporation, Seattle, WA). The goal of this study is to determine whether inhibition of TNF bioactivity can attenuate acute inflammation. The anti-inflammatory and adverse effects of etanercept, a recombinant TNF receptor fusion protein, will be evaluated using a model of tissue injury, the oral surgery model. Briefly, healthy volunteers referred for third molar extraction will undergo the surgical extraction of third molars with local anesthesia and conscious sedation. At the completion of the surgical procedure, a microdialysis probe will be placed under the mucogingival flap previously elevated for the surgical procedure and subjects will be observed for pain and swelling over the course of four hours following surgery. Tissue biopsies prior to and following surgery will be obtained from the buccal mucosa. Etanercept or control will be administered parenterally one hour prior to surgery. Tissue levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will be measured at time intervals postoperatively. Pain and swelling will be assessed postoperatively over the course of four hours and at 48 hours. Demonstration of amelioration of pain, swelling, and/or changes in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect of etanercept. Since the fusion protein (hereafter, TNFR:fc) specifically binds TNF-alpha and prevents its interaction with cellular receptors, changes in the inflammatory cascade and clinical endpoints of inflammation may provide insight into role of TNF-alpha in the pathophysiology of acute inflammation and its clinical sequela.