Zoumbos N C, Gascon P, Djeu J Y, Young N S
Proc Natl Acad Sci U S A. 1985 Jan;82(1):188-92. doi: 10.1073/pnas.82.1.188.
We have investigated interferon as a mediator of hematopoietic suppression in bone marrow failure. Interferon production by stimulated peripheral blood mononuclear cells from patients with aplastic anemia was significantly higher than that observed in controls; spontaneous interferon production by these cells was also high for more than half of aplastic anemia patients. Circulating interferon, not detectable in normal individuals, was detected in 10 of 24 patients. Interferon is a potent inhibitor of hematopoietic cell proliferation and, therefore, may be the mediator of suppression in many in vitro models employing patients' cells and sera. The possible pathogenic importance of interferon in aplastic anemia was suggested by an increase in hematopoietic colony formation in vitro after exposure of bone marrow cells to antiinterferon antisera (277 +/- 71% increase for patients compared to 1.6 +/- 1.6% for normal individuals). Interferon levels in the bone marrow sera of aplastic anemia patients were high (mean = 203 international units (IU)/ml, n = 8), even in comparison to circulating levels in the same patients. Normal bone marrow sera also contained measurable interferon but at lower levels (41 IU/ml, n = 16), indicating that interferon may be a normal bone marrow product. High concentration of bone marrow interferon, possibly due to abnormal immunologic activity or a reaction to virus infection of the bone marrow, may mediate hematopoietic suppression in aplastic anemia patients.
我们研究了干扰素作为骨髓衰竭中造血抑制介质的作用。再生障碍性贫血患者受刺激的外周血单个核细胞产生的干扰素明显高于对照组;超过半数的再生障碍性贫血患者这些细胞的自发干扰素产生也很高。在24例患者中有10例检测到循环干扰素,而正常个体中未检测到。干扰素是造血细胞增殖的强效抑制剂,因此,在许多使用患者细胞和血清的体外模型中可能是抑制作用的介质。将骨髓细胞暴露于抗干扰素抗血清后,体外造血集落形成增加,提示干扰素在再生障碍性贫血中可能具有致病重要性(患者增加277±71%,而正常个体增加1.6±1.6%)。再生障碍性贫血患者骨髓血清中的干扰素水平很高(平均 = 203国际单位(IU)/毫升,n = 8),甚至与同一患者的循环水平相比也是如此。正常骨髓血清中也含有可测量的干扰素,但水平较低(41 IU/毫升,n = 16),表明干扰素可能是正常的骨髓产物。骨髓中高浓度的干扰素,可能由于异常的免疫活性或对骨髓病毒感染的反应,可能介导再生障碍性贫血患者的造血抑制。