IADR Abstract Archives

Etanercept Demonstrates Acute Anti-inflammatory Effects

Background: Acute inflammation is characterized by the expression and actions of inflammatory mediators known to interact with peripheral nociceptors to amplify pain. TNF-alpha is a cytokine associated with many chronic inflammatory conditions; however, its role in acute inflammation has not been elucidated. Etanercept is a highly specific fusion protein that binds TNF and is approved for the treatment of some chronic inflammatory disorders. There are no published reports on the efficacy of etanercept in acute inflammation in humans.

Objective: This study tested the acute anti-inflammatory effect of etanercept using functional assays in the oral surgery model of tissue injury.

Methods: Subjects underwent extraction of impacted third molars in a randomized, double-blind, within-subject designed study. Tissue biopsies and ultrasound images were obtained before surgery and at 48 hr to quantify cellular infiltrate and the clinical sign of edema. Submucosal perfusate from the surgical site was obtained by microdialysis for four hrs postoperatively and pain report was recorded at each sample collection interval on the day of surgery, as well as at 48 hr.

Results: The positive control ketorolac significantly suppressed eicosanoids as measured by EIA (p < 0.001) and significantly suppressed pain (p < 0.003), demonstrating assay sensitivity. PGE2 was also significantly suppressed by etanercept compared to placebo (p < 0.05) accompanied by a significant decrease in pain report (p < 0.05) over the first 4 hr postoperatively. Pain report at 48 hrs was not different. Cellular infiltrate was significantly higher (p < 0.001) at 48 hr in all groups, with no significant difference between drug and placebo. Ultrasound measurement of edema demonstrated assay sensitivity, with the ability to detect a greater amount of swelling at 48 hr.

Conclusion: Suppression of molecular and clinical measures for inflammation in an acute injury model suggests a role for TNF-alpha in acute inflammation.


IADR/PER General Session
2003 IADR/PER General Session (Goteborg, Sweden)
Goteborg, Sweden
2003
129
Pharmacology, Therapeutics, & Toxicology
  • Gordon, Sharon M  ( NIDCR, NIH, Washington, DC, USA )
  • Wahl, Sharon M.  ( NIDCR, NIH, Bethesda, MD, USA )
  • Picco, Christine  ( NIDCR, NIH, Bethesda, MD, USA )
  • Sonies, Barbara  ( National Institutes of Health, Bethesda, MD, USA )
  • Miller, Jeri  ( National Institutes of Health, Bethesda, MD, USA )
  • Castillo, Juan  ( National Institutes of Health, Bethesda, MD, USA )
  • Dionne, Raymond A.  ( NIDCR, NIH, Bethesda, MD, USA )
    • Oral
    Oral Health/Pharmacology
    06/25/2003