title: Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans.
abstract: 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 E2 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 E2 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 E2 concentration after surgery; interleukin 1beta and tumor necrosis factor alpha were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1beta; tumor necrosis factor alpha decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 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 E2.
  
  
  CONCLUSIONS
  These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.
authors.affiliation: Department of Anesthesiology, Rush University Medical Center, Chicago, Illinois 60612, USA. asokumar@aol.com
authors.forename: Asokumar
authors.initials: A
authors.lastname: Buvanendran
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kroin
authors.forename: Richard A
authors.initials: RA
authors.lastname: Berger
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Chiranjeev
authors.initials: C
authors.lastname: Saha
authors.forename: Corina
authors.initials: C
authors.lastname: Negrescu
authors.forename: Mario
authors.initials: M
authors.lastname: Moric
authors.forename: Marco S
authors.initials: MS
authors.lastname: Caicedo
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Tuman
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip; D002490:Central Nervous System / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D007378:Interleukins / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D008875:Middle Aged; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D015232:Dinoprostone