Mongan A E, Ramdahin S, Warrington R J
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Scand J Immunol. 1997 Oct;46(4):406-12. doi: 10.1046/j.1365-3083.1997.d01-140.x.
It has been previously reported that the production of interleukin-6 (IL-6) is often enhanced in systemic lupus erythematosus (SLE). The authors examined the secretion of IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor, IL-1 alpha and IL-4 by B cells and monocytes from lupus patients and compared this to the production in normal controls and in rheumatoid arthritis patients. IL-6 production was increased an average of 3.4-fold compared to that in normal subjects and 8.4-fold compared to rheumatoid arthritis patients. In SLE, a strongly positive correlation was found between the levels of IL-6 and TNF-alpha (R = 0.8987, P = 0.002). Since production of both IL-6 and TNF-alpha is regulated by IL-10, the enhancement of the production of these cytokines could reflect a defect in either IL-10 production or responsiveness. However, spontaneous production of IL-10 was enhanced in cultures of B cells and monocytes from lupus patients, compared to normal controls, the levels being increased 3.1- to 6-fold for monocytes and B cells, respectively. The finding of increased secretion of these cytokines implies an abnormality in IL-10-mediated suppression in SLE. To assess this possibility, the authors examined recombinant human IL-10-mediated suppression of IL-6 production by monocytes and B cells from lupus patients, compared to normal controls, and found that whereas IL-10 caused a concentration-dependent suppression of IL-6 production in normal B cells and monocytes, this suppression was deficient in B cells and monocytes from lupus patients. In SLE, it therefore appears that there may be an intrinsic defect in IL-10-induced suppression of cytokine synthesis. This could explain the increased levels of IL-10 and IL-6 found in this condition, and may also be responsible for the characteristic polyclonal B-cell activation that is seen.
此前有报道称，系统性红斑狼疮（SLE）患者体内白细胞介素-6（IL-6）的生成常常增强。作者检测了狼疮患者B细胞和单核细胞分泌IL-6、肿瘤坏死因子-α（TNF-α）、粒细胞巨噬细胞集落刺激因子、IL-1α和IL-4的情况，并将其与正常对照者及类风湿关节炎患者的分泌情况进行比较。与正常受试者相比，IL-6的生成平均增加了3.4倍，与类风湿关节炎患者相比增加了8.4倍。在SLE患者中，IL-6水平与TNF-α水平之间存在强正相关（R = 0.8987，P = 0.002）。由于IL-6和TNF-α的生成均受IL-10调控，这些细胞因子生成的增强可能反映出IL-10生成或反应性方面的缺陷。然而，与正常对照者相比，狼疮患者B细胞和单核细胞培养物中IL-10的自发生成增强，单核细胞和B细胞的水平分别增加了3.1至6倍。这些细胞因子分泌增加的发现意味着SLE中IL-10介导的抑制存在异常。为评估这种可能性，作者检测了重组人IL-10对狼疮患者单核细胞和B细胞IL-6生成的介导抑制作用，并与正常对照者进行比较，发现虽然IL-10可导致正常B细胞和单核细胞中IL-6生成呈浓度依赖性抑制，但狼疮患者的B细胞和单核细胞中这种抑制作用存在缺陷。因此，在SLE中，IL-10诱导的细胞因子合成抑制可能存在内在缺陷。这可以解释在这种情况下发现的IL-10和IL-6水平升高，也可能是所见特征性多克隆B细胞活化的原因。
