Lundberg I, Brengman J M, Engel A G
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
J Neuroimmunol. 1995 Dec;63(1):9-16. doi: 10.1016/0165-5728(95)00122-0.
We investigated the profiles of cytokine mRNA expression in muscle in 15 cases of inflammatory myopathy (IM) (5 each of polymyositis, inclusion body myositis, and dermatomyositis) and in 10 controls (5 of Duchenne dystrophy and 5 non-weak subjects). Expressions of the predominantly T cell-derived cytokines (interleukin (IL)-2, IL-4, IL-5, and interferon-gamma (IFN-gamma), of the predominantly macrophage-derived cytokines (IL-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha)), as well as cytokines that can be of either T cell or macrophage origin (granulocyte-macrophage colony stimulating factor (GM-CSF) and transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2), were monitored by the reverse transcriptase-PCR method. The expression of T cell cytokine mRNAs for IL-2, IL-5, and IFN-gamma was generally weak or inconsistent. IL-4 mRNA expression was consistently moderate to strong in polymyositis but generally weak or absent in the other IMs. The expression of macrophage cytokine mRNAs for IL-1 alpha and IL-1 beta was weak or absent in all cases. Variable TNF-alpha mRNA expression was observed in 12 of 15 IM cases and faint or weak expression in 5 of 10 controls. Very strong GM-CSF expression was detected, but only on boosted PCR, in 12 of 15 cases of IM but in none of the controls. IL-6 was expressed only weakly or inconsistently. In contrast to the variable expression of several of the above mentioned cytokine mRNAs, all IM specimens strongly expressed TGF-beta 1 mRNA and 12 of 15 strongly expressed TGF-beta 2 mRNA. Thus, with the exception of IL-4 expression in polymyositis, a similar pattern of cytokine mRNA expression exists in the different types of IMs. Moreover, this pattern resembles that detected in non-weak and DD controls, although expression is generally weaker in the non-weak controls. The findings suggest that in IM muscle a sustained secretion of cytokines by T cells or of IL-1 by macrophages is not a prerequisite for operation of the immune effector response and that muscle may not be the site of ongoing sensitization.
我们研究了15例炎性肌病(IM)(多发性肌炎、包涵体肌炎和皮肌炎各5例)以及10例对照(5例杜氏肌营养不良症患者和5例非肌无力受试者)肌肉中细胞因子mRNA的表达情况。采用逆转录聚合酶链反应(RT-PCR)法监测主要由T细胞产生的细胞因子(白细胞介素(IL)-2、IL-4、IL-5和干扰素-γ(IFN-γ))、主要由巨噬细胞产生的细胞因子(IL-1、IL-6和肿瘤坏死因子-α(TNF-α))以及可能由T细胞或巨噬细胞产生的细胞因子(粒细胞-巨噬细胞集落刺激因子(GM-CSF)、转化生长因子β1(TGF-β1)和TGF-β2)的表达。IL-2、IL-5和IFN-γ的T细胞细胞因子mRNA表达通常较弱或不一致。IL-4 mRNA表达在多发性肌炎中持续中等至强烈,但在其他IM中通常较弱或缺失。IL-1α和IL-1β的巨噬细胞细胞因子mRNA表达在所有病例中均较弱或缺失。15例IM病例中有12例观察到TNF-α mRNA表达可变,10例对照中有5例表达微弱或较弱。仅在增强PCR时,15例IM病例中有12例检测到非常强烈的GM-CSF表达,而对照中均未检测到。IL-6仅表达微弱或不一致。与上述几种细胞因子mRNA的可变表达相反,所有IM标本均强烈表达TGF-β1 mRNA,15例中有12例强烈表达TGF-β2 mRNA。因此,除了多发性肌炎中IL-4的表达外,不同类型的IM中存在相似的细胞因子mRNA表达模式。此外,尽管在非肌无力对照中表达通常较弱,但这种模式与在非肌无力和杜氏肌营养不良症对照中检测到的模式相似。研究结果表明,在IM肌肉中,T细胞持续分泌细胞因子或巨噬细胞持续分泌IL-1并非免疫效应反应发挥作用的先决条件,并且肌肉可能不是持续致敏的部位。