Molloy R G, Mannick J A, Rodrick M L
Department of Surgical Immunology, Harvard Medical School, Boston, Massachusetts.
Br J Surg. 1993 Mar;80(3):289-97. doi: 10.1002/bjs.1800800308.
Tissue injury and infection produce significant alterations in host metabolic and immune homeostasis. It is increasingly clear that many of these changes result from a complex cascade of mononuclear phagocyte-derived endogenous mediators. Among the more important is a group of host proteins called cytokines, which play an integral role in mediating the host response to tissue injury and infection. Of these proteins, tumour necrosis factor (TNF) and interleukin (IL) types 1 and 6 have received much attention for their pathophysiological roles in infection and trauma. Evidence is reviewed for the involvement of these cytokines in the characteristic alterations in the metabolic and immune responses to such injury. These endogenous mediators initiate an integrated fuel substrate and hormonal adjustment to trauma and sepsis, and help to provide optimal metabolic homeostasis for systemic host defences. Widespread tissue injury, especially when associated with fulminant sepsis, may, however, precipitate massive release of TNF, IL-1 and IL-6, triggering a series of reactions involving multiple organs, and culminating in the 'sepsis syndrome'. New therapies designed to downregulate this aberrant response, either by neutralizing endotoxin directly or by blocking the release or actions of these cytokines, are reviewed. Although these treatments hold much promise for the future management of severely traumatized and infected patients, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended.
组织损伤和感染会使宿主的代谢和免疫稳态发生显著改变。越来越清楚的是，许多这些变化是由单核吞噬细胞衍生的内源性介质的复杂级联反应引起的。其中更重要的是一组称为细胞因子的宿主蛋白，它们在介导宿主对组织损伤和感染的反应中起着不可或缺的作用。在这些蛋白质中，肿瘤坏死因子（TNF）以及1型和6型白细胞介素（IL）因其在感染和创伤中的病理生理作用而备受关注。本文综述了这些细胞因子参与此类损伤的代谢和免疫反应特征性改变的证据。这些内源性介质启动了对创伤和脓毒症的综合燃料底物和激素调节，并有助于为全身宿主防御提供最佳的代谢稳态。然而，广泛的组织损伤，尤其是与暴发性脓毒症相关时，可能会促使TNF、IL-1和IL-6大量释放，引发一系列涉及多个器官的反应，并最终导致“脓毒症综合征”。本文综述了旨在通过直接中和内毒素或阻断这些细胞因子的释放或作用来下调这种异常反应的新疗法。尽管这些治疗方法对严重创伤和感染患者的未来治疗具有很大的前景，但在推荐广泛临床应用之前，需要对治疗的益处和并发症进行仔细评估。
