Linker-Israeli M, Honda M, Nand R, Mandyam R, Mengesha E, Wallace D J, Metzger A, Beharier B, Klinenberg J R
Department of Medicine, Cedars-Sinai Medical Center Research Institute, California 90048, USA.
Clin Immunol. 1999 Apr;91(1):6-16. doi: 10.1006/clim.1998.4680.
The elevated expression of IL-6 and IL-10 may have an important role in SLE pathogenesis. IL-6 production by normal monocytes can be inhibited by IL-10, and it has been suggested that SLE monocytes are refractory to this negative signal. To examine this possibility, the effects of regulatory factors on IL-6 expression by SLE PBMC (N = 51) were compared to effects on control PBMC (N = 21). We found that (1) exogenous rIL-10 and rIL-4 mediated reduction of constitutive and lectin-induced IL-6 in monocytes of SLE patients as effectively as that of controls; (2) IL-6 mRNA decay was significantly delayed in SLE with active disease (P < 0.001); (3) adding rIL-10 or neutralizing endogenous IL-1 beta and TNF-alpha down-regulated IL-6 mainly by destabilizing IL-6 transcripts, whereas exogenous IL-4 and TGF beta 1 down-regulated IL-6 transcriptionally; (4) time kinetics and levels of IL-10 were lower than those of IL-6 and IL-1 beta. Thus, contrary to a previous report, IL-6 production by SLE PBMC responds normally to regulatory signals, and the IL-6 overexpression in SLE may be due, at least in part, to the kinetics and availability of regulatory cytokines.
IL-6和IL-10的表达升高可能在系统性红斑狼疮（SLE）发病机制中起重要作用。正常单核细胞产生的IL-6可被IL-10抑制，有人提出SLE单核细胞对这种负信号不敏感。为检验这种可能性，将调节因子对SLE患者外周血单个核细胞（PBMC，N = 51）IL-6表达的影响与对对照PBMC（N = 21）的影响进行了比较。我们发现：（1）外源性重组人IL-10（rIL-10）和重组人IL-4（rIL-4）介导的SLE患者单核细胞中组成性和凝集素诱导的IL-6减少与对照组一样有效；（2）活动性疾病的SLE患者中IL-6 mRNA降解显著延迟（P < 0.001）；（3）添加rIL-10或中和内源性IL-1β和肿瘤坏死因子-α（TNF-α）主要通过使IL-6转录本不稳定而下调IL-6，而外源性IL-4和转化生长因子-β1（TGF-β1）则通过转录下调IL-6；（4）IL-10的时间动力学和水平低于IL-6和IL-1β。因此，与先前的报道相反，SLE患者PBMC产生的IL-6对调节信号反应正常，SLE中IL-6的过表达可能至少部分归因于调节性细胞因子的动力学和可用性。
