Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
Ann Rheum Dis. 2012 Jun;71(6):1055-63. doi: 10.1136/annrheumdis-2011-200495. Epub 2012 Jan 20.
To investigate the expression of interleukin (IL)-15 and IL-15 receptor α (IL-15Rα) in muscle tissue from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive (IS) treatment.
Muscle biopsies from 17 patients before and after conventional IS treatment and seven healthy individuals were investigated by immunohistochemistry using antibodies against IL-15 and IL-15Rα. Quantification was performed by computerised image analysis. Cellular localisation of IL-15 was determined by double immunofluorescence. Clinical outcome was measured by the functional index and serum creatine kinase. Human myotubes were cultured and IL-15 staining was performed by immunocytochemistry.
IL-15 was observed in mononuclear inflammatory cells of muscle tissue while IL-15Rα was localised to mononuclear inflammatory cells, capillaries and large vessels. Double staining showed localisation of IL-15 to CD163+ macrophages. A significantly larger number of IL-15 and IL-15Rα-positive cells were seen in muscle tissue of patients compared with healthy individuals. Baseline IL-15 expression correlated negatively with improvement in muscle function. After conventional IS treatment, a significantly lower number of IL-15 and IL-15Rα-positive cells was found. However, compared with controls, eight of 17 patients still had more IL-15-positive cells and less muscle function improvement was shown in this group of patients, both in short-term and long-term observations. Human differentiated myotubes were negative for IL-15 staining.
IL-15 and its receptor are expressed in the muscle tissue of patients with myositis and IL-15 expression is correlated with improvement in muscle function. IL-15 may play a role in the pathogenesis of myositis and could be a biological treatment target, at least in a subgroup of patients with polymyositis or dermatomyositis.
研究白细胞介素 (IL)-15 和 IL-15 受体 α (IL-15Rα) 在多发性肌炎或皮肌炎患者接受常规免疫抑制 (IS) 治疗前后肌肉组织中的表达。
采用免疫组织化学法检测 17 例多发性肌炎或皮肌炎患者常规 IS 治疗前后及 7 例健康对照者肌肉活检组织中 IL-15 和 IL-15Rα 的表达，并用计算机图像分析进行定量分析。采用双免疫荧光法确定 IL-15 的细胞定位。通过功能指数和血清肌酸激酶测量临床结果。培养人肌管并进行免疫细胞化学染色以检测 IL-15 染色。
IL-15 存在于肌肉组织的单核炎性细胞中，而 IL-15Rα 则定位于单核炎性细胞、毛细血管和大血管。双染显示 IL-15 定位于 CD163+巨噬细胞。与健康对照者相比，患者肌肉组织中 IL-15 和 IL-15Rα 阳性细胞的数量明显更多。基线时 IL-15 表达与肌肉功能改善呈负相关。经常规 IS 治疗后，IL-15 和 IL-15Rα 阳性细胞的数量明显减少。然而，与对照组相比，17 例患者中有 8 例仍有更多的 IL-15 阳性细胞，且在短期和长期观察中，该组患者的肌肉功能改善程度较小。分化的人肌管对 IL-15 染色呈阴性。
IL-15 和其受体在肌炎患者的肌肉组织中表达，IL-15 的表达与肌肉功能的改善相关。IL-15 可能在肌炎的发病机制中发挥作用，并且可能成为至少一部分多发性肌炎或皮肌炎患者的生物治疗靶点。
