Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans

Background: The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E. and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. Methods: Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E-2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. Results: Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E-2 concentration after surgery; interleukin 113 and tumor necrosis factor a were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E-2, interleukin 6, interleukin 8, and interleukin 1 beta; tumor necrosis factor a decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E-2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E-2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E-2. Conclusions: These results suggest that upregulation of prostaglandin E-2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.