Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Ann N Y Acad Sci. 2009 Dec;1182:58-68. doi: 10.1111/j.1749-6632.2009.05068.x.
Interferons (IFNs) are widely used in therapy for viral, neoplastic, and inflammatory disorders, but clinical response varies among patients. The biological basis for variable clinical response is not known. We determined the primary molecular response to IFN-beta (IFN-beta) injections in 35 treatment-naïve multiple sclerosis (MS) patients using a customized cDNA macroarray with 186 interferon-stimulated genes (ISGs). Our results revealed striking interindividual heterogeneity, both in the magnitude as well as the nature of the primary molecular response to IFN-beta injections. Despite marked between-subject variability in the molecular response, responses within individual subjects were stable over a 6-month interval. Our data suggest that clinical response to IFN-beta therapy for MS differs among patients because of qualitative rather than quantitative variability in the primary molecular response to the drug.
干扰素 (IFNs) 广泛应用于病毒、肿瘤和炎症性疾病的治疗,但患者之间的临床反应存在差异。导致这种临床反应差异的生物学基础尚不清楚。我们使用带有 186 个干扰素刺激基因 (ISGs) 的定制 cDNA 微阵列,对 35 名未经治疗的多发性硬化症 (MS) 患者进行 IFN-β (IFN-β) 注射的主要分子反应进行了测定。我们的结果显示,尽管 IFN-β 注射的分子反应存在明显的个体间异质性,但个体内的反应在 6 个月的间隔内是稳定的。我们的数据表明,MS 患者对 IFN-β 治疗的临床反应存在差异,这是由于对药物的主要分子反应存在定性而非定量的变异性。