MYELOPOIETIC STIMULATION FOLLOWING BURN INJURY

烧伤伴随着宿主防御机制的显著变化。 尽管局部和全身抗菌治疗取得了进展， 伤口闭合技术，脓毒症仍是死亡的主要原因 在严重烧伤的病人身上。成功的主机防御和修复后 热损伤在一定程度上取决于是否有足够的 功能正常的高度活动的髓系细胞的数量，如 粒细胞、单核细胞和巨噬细胞。然而，骨髓抑制有 在热损伤后表现出来，感觉部分是 造成烧伤伤者对 感染。重组造血生长的最新研究进展 因子允许调节髓系细胞的数量和功能 元素，试图提高寄主对感染的抵抗力。我们 建议系统分析烧伤的影响以及 细菌烧伤创面接种对小鼠骨髓细胞反应的影响。我们 将寻求确定人类重组粒细胞的能力 集落刺激因子(G-CSF)显著提高存活率和 增强损伤后的髓系反应。将对G-CSF进行检测 单用及与粒细胞集落刺激因子(GM- 和白细胞介素1β(1L-1β)和/或常规 改善骨髓抑制和改变的抗菌治疗 结果。与大量甲基溴相关的潜在毒性 激活的中性粒细胞和单核细胞将被系统地分析 进行完整的尸检、组织病理学分析和 支气管肺灌洗液测定。这些研究将提供 进一步描述以下骨髓生成反应的信息 烧伤创面感染与烧伤的安全性和有效性 造血刺激剂在烧伤反应中的作用 代表了对创伤和败血症的典型反应，因此， 在烧伤研究中获得的知识适用于 手术后和创伤后感染并发症。

Burn injury is accompanied by marked changes in host defense mechanisms. Despite advances in topical and systemic antimicrobial therapy and techniques of wound closure, sepsis remains the main cause of mortality in severely burned patients. Successful host defense and repair after thermal injury is, in part, dependent on the presence of adequate numbers of functionally competent highly motile myeloid cells such as granulocytes, monocytes and macrophages. However, myelosuppression has been demonstrated following thermal injury and is felt to be in part responsible for the altered susceptibility of burn injured victims to infection. The recent availability of recombinant hematopoietic growth factors allows modulation of the numbers and functions of myeloid elements in an attempt to improve host resistance to infection. We propose to systematically analyze the effects of burn injury as well as bacterial burn wound seeding on the myelopoietic response in mice. We will seek to determine the capability of human recombinant granulocyte colony-stimulating factor (G-CSF) to significantly improve survival and augment the myeloid response following injury. G-CSF will be tested alone and in combination with granulocyte colony-stimulating factor (GM- CSF) and Interleukin-1 beta (1L-1 beta) and/or conventional antimicrobial therapy on ameliorating myelosuppression and altering outcome. Potential toxicities associated with large numbers of activated neutrophils and monocytes will be systematically analyzed by performing complete necropsy, histopathologic analysis and bronchopulmonary lavage fluid assay. These studies will provide information to further characterize the myelopoietic response following burn injury and infection of the burn wound, the safety and efficacy of hematopoietic stimulants in the setting of response to burn injury represents a prototypical response to trauma and sepsis and, therefore, knowledge gained in the study of burn injury is applicable to postsurgical and posttraumatic infectious complications.