Adams E M, Kirkley J, Eidelman G, Dohlman J, Plotz P H
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Assoc Am Physicians. 1997 May;109(3):275-85.
Cytokines and chemokines that upregulate major histocompatibility complex class I antigens, recruit lymphocytes, and enhance T-cell-mediated myotoxicity may be important in the pathogenesis of dermatomyositis and polymyositis. We searched for cytokine and chemokine transcripts in inflammatory muscle specimens from 14 newly diagnosed or treated patients. Control specimens from six patients without inflammatory muscle disease were analyzed for transcripts of interleukins-1 beta, -2, -4, -6, -10, and -15, and interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta 1, macrophage inflammatory proteins-1 alpha and -1 beta (MIP-1 alpha, MIP-1 beta), and the chemokine "regulated on activation, normally T expressed and secreted" (RANTES). Surprisingly, the proinflammatory and lymphocyte cytokines were detected only sporadically in myositis muscle specimens, and their presence did not correlate with disease activity or treatment status of the patient. In contrast, MIP-1 alpha and MIP-1 beta were detected in 13 and 6 myositis biopsies, respectively, and RANTES, another beta (CC) chemokine, was detected in eight myositis biopsies. This study and other reports of low levels of acute-phase cytokines in myositis patients suggest that the proinflammatory cytokines do not play a major role in ongoing muscle damage. The CC chemokines studied here, in particular MIP-1 alpha, might contribute to ongoing muscle inflammation, and the pathogenesis of inflammation in myositis may follow a previously unrecognized pathway.
上调主要组织相容性复合体I类抗原、募集淋巴细胞并增强T细胞介导的肌毒性的细胞因子和趋化因子可能在皮肌炎和多发性肌炎的发病机制中起重要作用。我们在14例新诊断或正在接受治疗的患者的炎性肌肉标本中查找细胞因子和趋化因子转录本。对6例无炎性肌肉疾病患者的对照标本进行白细胞介素-1β、-2、-4、-6、-10和-15、干扰素-γ、肿瘤坏死因子-α、转化生长因子-β1、巨噬细胞炎性蛋白-1α和-1β（MIP-1α、MIP-1β）以及趋化因子“活化时上调、正常T细胞表达和分泌”（RANTES）转录本的分析。令人惊讶的是，促炎和淋巴细胞细胞因子仅偶尔在肌炎肌肉标本中检测到，其存在与患者的疾病活动或治疗状态无关。相比之下，分别在13例和6例肌炎活检标本中检测到MIP-1α和MIP-1β，另一种β（CC）趋化因子RANTES在8例肌炎活检标本中检测到。这项研究以及其他关于肌炎患者急性期细胞因子水平较低的报告表明，促炎细胞因子在持续的肌肉损伤中不发挥主要作用。本文研究的CC趋化因子，尤其是MIP-1α，可能导致持续的肌肉炎症，肌炎炎症的发病机制可能遵循一条以前未被认识的途径。
