title: Neuroendocrine responses mediate macrophage function after trauma.
abstract: BACKGROUND
  Clearly understanding the interactions between macrophage (M phi)-generated inflammatory mediators and the neuroendocrine system in regulating immune function after traumatic injury may aid in reversing trauma-mediated immune dysfunction and diminish the incidence and severity of infection in the traumatized patient.
  
  
  METHODS
  Trauma consisted of an open femur fracture and 40% retro-orbital hemorrhage (Trauma) or anesthesia alone (Control). Female Balb/C mice (6-8 weeks) with intact adrenal glands (Intact) or a bilateral adrenalectomy (ADX) were used. For glucocorticoid studies, corticosterone or a vehicle was administered via intraperitoneal (ip) injection 2 hours before the trauma. Splenic M phis were harvested and prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6) production, and mRNA, cyclooxygenase-2 (COX-2) protein, and nuclear factor kappa B (NF-kappa B) activity were measured.
  
  
  RESULTS
  M phi, PGE(2) and IL-6 production in Trauma+Intact mice was significantly increased compared with Control+Intact mice. Adrenalectomy decreased these levels to Control levels. Similar changes were observed for COX-2 and IL-6 expression. M phi nuclear NF-kappa B levels were increased in Trauma+Intact mice compared with controls. Adrenalectomy abrogated this increase. Treating Trauma+Intact mice with RU-486 did not restore PGE(2) and IL-6 production or COX-2 and IL-6 messenger RNA to control levels. Administering exogenous glucocorticoid to Intact mice did not increase PGE(2) and IL-6 production or COX-2 and IL-6 mRNA to Trauma levels.
  
  
  CONCLUSIONS
  The neuroendocrine system upregulates certain M phi inflammatory mediators, including PGE(2), IL-6, and NF-kappa B, after trauma. This upregulation does not seem to be mediated via glucocorticoids and possibly may be mediated via catecholamines. Elucidation of the interactions between the neuroendocrine system, the immune system, and inflammatory mediator secretion might provide novel therapeutic strategies for the injured patient.
authors.affiliation: Department of Surgery, Weill Medical College of Cornell University/New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Sirish
authors.initials: S
authors.lastname: Maddali
authors.forename: Philip P
authors.initials: PP
authors.lastname: Stapleton
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Freeman
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Smyth
authors.forename: Michael
authors.initials: M
authors.lastname: Duff
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Yan
authors.forename: John M
authors.initials: JM
authors.lastname: Daly
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000503:physiopathology*; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000473:pathology / Q000503:physiopathology; D014947:Wounds and Injuries / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D015735:Mifepristone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003345:Corticosterone