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<.01) and rofecoxib (p<.05) treatment. Three other enzymes related to PG production; sPLA2IIA, mPGES and cPGES, were significantly increased (ibuprofen > 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: