Molloy R G, Holzheimer R, Nestor M, Collins K, Mannick J A, Rodrick M L
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Br J Surg. 1995 Jun;82(6):770-6. doi: 10.1002/bjs.1800820618.
Thermal injury is associated with reduced colony-stimulating activity, which correlates with increased susceptibility to infection. To assess the effect of therapeutic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF), 8-week old anaesthetized mice were subjected to either a 20 per cent body surface burn or a sham burn. Animals were subsequently treated with either vehicle or a range of doses of GM-CSF (10-1000 ng) with or without indomethacin (5 micrograms). Sepsis was induced by caecal ligation and puncture on day 10 after injury. Survival was significantly better in animals treated with 200 ng GM-CSF on days 5-9 after the burn. Concanavalin A-stimulated T cell proliferation and interleukin (IL) 2 production were significantly depressed after burn injury. In vivo therapy with 200 ng GM-CSF, however, led to a significant improvement in both of these parameters of T cell function. These data suggest that GM-CSF has a potential therapeutic role in the prevention of death from burn sepsis and appears to act, at least in part, by restoring defective T cell proliferation and IL-2 production.
热损伤与集落刺激活性降低有关,而集落刺激活性降低与感染易感性增加相关。为了评估粒细胞-巨噬细胞集落刺激因子(GM-CSF)治疗性给药的效果,对8周龄的麻醉小鼠进行20%体表烧伤或假烧伤。随后,动物接受载体或一系列剂量的GM-CSF(10 - 1000 ng)治疗,同时或不使用吲哚美辛(5微克)。在损伤后第10天通过盲肠结扎和穿刺诱导脓毒症。烧伤后第5 - 9天,接受200 ng GM-CSF治疗的动物存活率显著更高。烧伤后伴刀豆球蛋白A刺激的T细胞增殖和白细胞介素(IL)-2产生显著降低。然而,体内给予200 ng GM-CSF导致T细胞功能的这两个参数都有显著改善。这些数据表明,GM-CSF在预防烧伤脓毒症死亡方面具有潜在的治疗作用,并且至少部分地通过恢复缺陷的T细胞增殖和IL-2产生发挥作用。