Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis.
Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis.
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DOI：
10.4049/jimmunol.147.1.117
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发表时间：
1991-07
影响因子：
4.4
通讯作者：
M. Linker‐Israeli;R. Deans;D. Wallace;J. Prehn;T. Ozeri-Chen;J. Klinenberg
中科院分区：
文献类型：
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作者：
M. Linker‐Israeli;R. Deans;D. Wallace;J. Prehn;T. Ozeri-Chen;J. Klinenberg
自发产生的IgG升高是SLE的特征。为了确定支持它的因素，我们在SLE患者中研究了IL-6， IL-6是一种在igg分泌细胞分化中起重要作用的细胞因子。70例患者血清中有63例血清IL-6高于正常水平（p < 0.05）。37例SLE活动性血清中有36例检测到IL-6滴度高于SLE非活动性血清（n = 33），高于健康对照组（n = 15） （p < 0.05）。11例患者中有11例新分离的PBMC中检测到IL-6 mRNA，但正常PBMC中未检测到IL-1 mRNA，而仅在活动性疾病患者中检测到IL-1 mRNA。IL-6活性在4例SLE患者的PBMC中恢复，但在4例正常供体中没有。免疫过氧化物酶法检测SLE单核细胞和淋巴细胞胞浆中IL-6的表达。当SLE PBMC在没有刻意刺激的短期培养中生长时，IL-6基因的表达迅速下降。因此，外源性IL-6可以增强SLE PBMC自发产生IgG。在存在针对IL-6、tnf - α或IL-1的中和抗体时，自发产生的IgG减少了20%至65%。相比之下，内源性IL-4的中和使产量增加了约40%。抗tnf - α处理降低了PBMC培养物中IL-6的含量，而抗il -4则增加了IL-6的含量，外源性IL-6逆转了抗tnf - α对IgG产生的影响。因此，tnf - α和IL-4的中和可能通过调节IL-6的合成/活性来影响IgG的产生。这些结果支持了内源性细胞因子失调促进SLE B细胞过度活跃的概念，并提示IL-6尤其具有重要的致病作用。
Elevated spontaneous IgG production is characteristic of SLE. To identify the factors that support it, IL-6, a cytokine with an important role in the differentiation of IgG-secreting cells, was studied in SLE patients. Higher than normal levels of IL-6 were found, by a B9 assay, in sera of 63 of 70 patients (p less than 0.05). IL-6 was detected in 36 of 37 active SLE sera in higher titers (p = 0.009) than those for inactive SLE (n = 33), which were higher (p less than 0.05) than healthy controls (n = 15). IL-6 mRNA was detected in freshly isolated PBMC of 11 of 11 patients but not in normal PBMC, whereas IL-1 mRNA was detected only in patients with active disease. IL-6 activity was recovered from PBMC of four SLE patients, but not from four normal donors. By immunoperoxidase, IL-6 was detected in the cytoplasm of SLE monocytes and lymphocytes. When SLE PBMC were grown in short term cultures with no deliberate stimulation, expression of the IL-6 gene declined rapidly. Accordingly, the spontaneous production of IgG by SLE PBMC could be enhanced by exogenous IL-6. Spontaneous IgG production was diminished by 20 to 65% in the presence of neutralizing antibodies to IL-6, TNF-alpha, or IL-1. In contrast, neutralization of endogenous IL-4 increased production by approximately 40%. Anti-TNF-alpha treatment decreased IL-6 content of PBMC cultures, whereas anti-IL-4 augmented it, and exogenous IL-6 reversed anti-TNF-alpha effects on IgG production. Therefore, it is possible that the neutralization of TNF-alpha and IL-4 affected IgG production by modulating the synthesis/activity of IL-6. These results support the concept that SLE B cell hyperactivity is promoted by dysregulation of endogenous cytokines and suggest that IL-6, in particular, has an important pathogenic role.