系统性红斑狼疮患者骨髓基质细胞生长特性与相关细胞因子的表达

背景：骨髓造血依赖于干细胞所处的造血微环境，其中基质细胞及多种细胞因子在造血中发挥着重要的调控作用。系统性红斑狼疮具有淋巴细胞亚群及相关细胞因子表达，其基质细胞及细胞因子的异常可能导致造血微环境异常，损伤造血功能。 目的：观察体外培养系统性红斑狼疮基质细胞的生长特性及细胞因子白细胞介素6、白细胞介素8的表达，探讨细胞因子与系统性红斑狼疮活动的关系，阐明系统性红斑狼疮慢性病贫血可能的病理机制。 设计、时间及地点：细胞学体外培养，病例-对照观察，于2008-01/12在大连医科大学附属第二医院血液风湿科及血液学实验室完成。 对象：选择大连医科大学附属第二医院血液风湿科收治的活动期系统性红斑狼疮患者15例(实验组)，男1例，女14例，中位年龄32(20~55)岁；合并慢性病贫血者7例，无贫血者8例。另选健康个体10名作为对照，男9名，女1名，中位年龄46(38~57)岁。 方法：取系统性红斑狼疮患者及健康对照者的骨髓液分离单个核细胞培养。 主要观察指标：系统性红斑狼疮患者及健康对照者骨髓基质细胞生长特性及体外培养上清白细胞介素6和白细胞介素8的水平。 结果：系统性红斑狼疮患者骨髓基质细胞较健康对照生长及集落形成均延后，合并慢性病贫血的系统性红斑狼疮患者更加明显，集落内各细胞排列欠规整有序。与健康对照者相比，系统性红斑狼疮患者骨髓基质细胞体外培养上清细胞因子白细胞介素6、白细胞介素8的表达显著升高(P < 0.01)，并且与系统性红斑狼疮的疾病活动呈正相关。 结论：由于系统性红斑狼疮基质细胞可能存在功能的缺陷，并且高表达细胞因子如白细胞介素6、白细胞介素8，损伤了骨髓微环境，最终导致系统性红斑狼疮患者造血功能异常。细胞因子可能成为系统性红斑狼疮疾病活动的标志。

Growth characteristics of bone marrow stromal cells and expression of growth-related cytokines in patients with systemic lupus erythematosus

BACKGROUND: Hematopoiesis of bone marrow depends on micro-enviroment for stem cells, in which stromal cells and a variety of cytokines play key roles in regulation of hematopoiesis. Imbalanced subpopulation of T-lymphocytes and abberant expression of cytokines in systemic lupus erythematosus (SLE) may lead to dysfunction of micro-environment for hematopoiesis and damage hematopoiesis function. OBJECTIVE: To elucidate the mechanisms of SLE complicated with anemia of chronic diseases by investigating the growth characteristics of stromal cells and expression of cytokines including interleukin (IL)-6 and IL-8 produced by stromal cells in SLE, and by exploring the relationship between cytokines and active SLE. DESIGN, TIME AND SETTING: Experiments for stromal cell culture in vitro and case-control were conducted at the Laboratory of Hematology, and Departments of Hematology and Rheumatology of Second Affiliated Hospital of Dalian Medical University from January to December in 2008. PARTICIPANTS: A total of 15 patients with active SLE were selected at the Departments of Rheumatology and Hematology of Second Affiliated Hospital of Dalian Medical University (experimental group), composing 1 male and 14 females, with the mean age of 32(20-55) years. There were 7 cases combined with anemia of chronic disease and 8 cases without anemia. An additional 10 healthy controls were enrolled, including 9 males and 1 female, with the mean age of 46 (38-57) years. METHODS: Mononeuclear cells of bone marrow aspirated from patients with active SLE and healthy controls were separated for culture in vitro. MAIN OUTCOME MEASURES: Growth characteristics and expression of IL-6 and IL-8 of stromal cells from bone marrow were measured in SLE patients and healthy controls. RESULTS: Growth and colony formation of stromal cells derived from patients with active SLE was postponed, and more delayed with anemia of chronic diseases, when compared with that of health controls. The stromal cells were well arranged in colonies. Compared with healthy controls, IL-6 and IL-8 levels in bone marrow stromal cell supernatant in vitro were significantly increased in SLE patients (P < 0.01), which was positively correlated with active phase of SLE. CONCLUSION: Impairment of bone marrow micro-enviroment, which was caused by defective stromal cells and abberant expression of cytokines including IL-6 and IL-8, finally lead to dysfunction of hematopoiesis of patients with SLE. Abberant expression of cytokines may develop into an indicator of active SLE.