Xing Z, Jordana M, Gauldie J, Wang J
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Histol Histopathol. 1999 Jan;14(1):185-201. doi: 10.14670/HH-14.185.
Cytokines are important soluble signalling molecules that dictate and coordinate inflammatory and immune responses. Further understanding the role of cytokines in the pathobiologic mechanisms of pulmonary inflammatory and immune diseases holds the key to the development of effective prophylactic and therapeutic strategies. In the last several years, the use of models of human pulmonary diseases established either in normal adult animals, mice deficient for a given immune cell type or cytokine, or mice engineered to overexpress a given cytokine, has remarkably facilitated our understanding of the mechanisms operating in human disease. Cytokines that are involved in pulmonary inflammatory and immune conditions may be generally divided into groups of pro-inflammatory, anti-inflammatory and growth-stimulatory cytokines. While pro-inflammatory cytokines can be detrimental under such severe conditions as endotoxemia and fibrosis, they are required in host resistance against infectious agents. Anti-inflammatory cytokines play an important role in controlling the extent of tissue inflammatory/immune responses. Overexpression of growth-stimulatory cytokines are often directly associated with tissue fibrotic responses. In this review, the findings attained from experimental models by us and others were discussed with emphasis on cellular and histopathologic alterations, cytokine-mediated molecular mechanisms and the prospects of cytokine-based therapeutic strategies. Due to the restrict space, we chose to focus only on models for endotoxic lung, endotoxemia, acute pulmonary infections by extracellular Gram-negative bacteria, chronic pulmonary infections by intracellular myco-bacteria, allergic airways inflammation and pulmonary fibrosis.
细胞因子是重要的可溶性信号分子，它们决定并协调炎症和免疫反应。进一步了解细胞因子在肺部炎症和免疫疾病病理生物学机制中的作用是开发有效预防和治疗策略的关键。在过去几年中，利用在正常成年动物、特定免疫细胞类型或细胞因子缺陷的小鼠或经基因工程改造过表达特定细胞因子的小鼠中建立的人类肺部疾病模型，极大地促进了我们对人类疾病发病机制的理解。参与肺部炎症和免疫状况的细胞因子通常可分为促炎、抗炎和生长刺激细胞因子组。虽然促炎细胞因子在内毒素血症和纤维化等严重情况下可能有害，但它们在宿主抵抗感染因子方面是必需的。抗炎细胞因子在控制组织炎症/免疫反应的程度方面发挥重要作用。生长刺激细胞因子的过表达通常与组织纤维化反应直接相关。在本综述中，我们讨论了我们自己以及其他人从实验模型中获得的研究结果，重点是细胞和组织病理学改变、细胞因子介导的分子机制以及基于细胞因子的治疗策略的前景。由于篇幅有限，我们选择仅关注内毒素性肺、内毒素血症、细胞外革兰氏阴性菌引起的急性肺部感染、细胞内分枝杆菌引起的慢性肺部感染、过敏性气道炎症和肺纤维化的模型。
