Effects of a dual COX-1/-2 inhibitor and a selective COX-2 inhibitor on pro-inflammatory gene expression in a clinical model of tissue injury

Abstract

Aims COX-1 expression is significantly decreased and COX-2 expression significantly increased 4 hours after surgery, but both return to pre-surgical levels by 48 hours in acutely inflamed human tissue (Lee et al, Soc. for Neurosci. 2004). This study evaluated the effect of a dual COX-1/-2 inhibitor (ibuprofen) and a selective COX-2 inhibitor (rofecoxib) on expression patterns of pro-inflammatory genes related to prostaglandin (PG) formation in the oral surgery model. Methods Pre- and post-surgical (48 hours) biopsy samples were taken from 64 patients undergoing surgical removal of impacted third molars. For evaluation of transcriptional activity, real-time PCR assays were performed. Results We found little detectable change in COX-1 expression but wide variation in COX-2 expression associated with drug administration: no change in the placebo group but increased COX-2 mRNA from ibuprofen (p rofecoxib > placebo), and 15-PGDH related to PG degradation, was significantly decreased (ibuprofen < rofecoxib < placebo). Conclusions These findings demonstrate that a dual COX-1/-2 inhibitor and a selective COX-2 inhibitor change expression patterns of pro-inflammatory genes following tissue injury that stimulate the arachidonic acid cascade and may attenuate the inhibitory actions of these drugs by increased production of PG. Clinical Pharmacology & Therapeutics (2005) 77, P9–P9; doi: 10.1016/j.clpt.2004.11.035