Neuroendocrine responses mediate macrophage function after trauma

Abstract

Background Clearly understanding the interactions between macrophage (Mφ)-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 Mφs 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-κB) activity were measured. Results Mφ, 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. Mφ nuclear NF-κB 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 Mφ inflammatory mediators, including PGE 2, IL-6, and NF-κB, 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.