Maddali Sirish, Stapleton Philip P, Freeman Tracy A, Smyth Gordon P, Duff Michael, Yan Zhaoping, Daly John M
Department of Surgery, Weill Medical College of Cornell University/New York Presbyterian Hospital, New York, NY, USA.
Surgery. 2004 Nov;136(5):1038-46. doi: 10.1016/j.surg.2004.03.001.
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.
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.
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.
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.
清楚了解巨噬细胞（M phi）产生的炎症介质与神经内分泌系统在创伤性损伤后调节免疫功能方面的相互作用，可能有助于逆转创伤介导的免疫功能障碍，并降低创伤患者感染的发生率和严重程度。
创伤包括开放性股骨骨折和40%眶后出血（创伤组）或仅行麻醉（对照组）。使用具有完整肾上腺（完整组）或双侧肾上腺切除术（ADX组）的雌性Balb/C小鼠（6 - 8周龄）。对于糖皮质激素研究，在创伤前2小时通过腹腔内（ip）注射给予皮质酮或赋形剂。收获脾脏M phi，测量前列腺素E（2）（PGE（2））和白细胞介素-6（IL-6）的产生，以及mRNA、环氧化酶-2（COX-2）蛋白和核因子κB（NF-κB）活性。
与对照组+完整组小鼠相比，创伤组+完整组小鼠中M phi、PGE（2）和IL-6的产生显著增加。肾上腺切除术将这些水平降低至对照组水平。COX-2和IL-6表达也观察到类似变化。与对照组相比，创伤组+完整组小鼠中M phi核NF-κB水平升高。肾上腺切除术消除了这种升高。用RU-486处理创伤组+完整组小鼠并未将PGE（2）和IL-6的产生或COX-2和IL-6信使RNA恢复至对照组水平。向完整组小鼠给予外源性糖皮质激素并未将PGE（2）和IL-6的产生或COX-2和IL-6 mRNA增加至创伤组水平。
创伤后神经内分泌系统上调某些M phi炎症介质，包括PGE（2）、IL-6和NF-κB。这种上调似乎不是通过糖皮质激素介导的，可能是通过儿茶酚胺介导的。阐明神经内分泌系统、免疫系统和炎症介质分泌之间的相互作用可能为受伤患者提供新的治疗策略。
