Genomic characterization of the inflammatory response initiated by surgical intervention and the effect of perioperative cyclooxygenase 2 blockade

Abstract

There are potentially deleterious sequelae of the physiologic response to surgical intervention. Some inflammatory cytokines can act as tumor growth factors, angiogenic and metastatic promoters, or both. Modulation of negative effects could improve outcomes from surgical intervention. The effects of surgical intervention on gene expression have not been fully elucidated. We assayed gene expression changes in an animal model of thoracotomy versus a sham operation and evaluated the ability of a cyclooxygenase inhibitor, celecoxib, to mediate these changes. Sixty adult male BALB/c mice were randomized into one of 3 experimental groups: sham operation with anesthesia only, thoracotomy incision, and thoracotomy incision with perioperative celecoxib administration. Six hours after surgical intervention, the animals were killed, and blood was collected. RNA pools from each group were labeled and hybridized to Mouse Whole Genome Microarrays. Gene expression profiles were analyzed to determine the effect of both surgical intervention and celecoxib treatment. Surgical intervention initiated a robust gene expression response. We identified 867 transcripts that were found to be statistically significant (corrected P < .05) and differentially expressed at least 2-fold in response to surgical intervention. Celecoxib had a profound effect on this response, preserving close to baseline levels of expression for most of those genes. Surgical intervention has a dramatic effect on the expression of genes related to the inflammatory response. Perioperative treatment with a cyclooxygenase 2 inhibitor abated many of these changes and might counteract many of the negative effects of the response to surgical intervention.