Ulvestad E, Aarseth J H, Vedeler C, Nyland H, Myhr K-M
Department of Microbiology and Immunology, The Gade Institute, Bergen, Norway.
Scand J Immunol. 2004 Jan;59(1):103-8. doi: 10.1111/j.0300-9475.2004.01360.x.
Multiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon-alpha2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: -0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment-mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 x 106 lymphocytes/ml (CI: -0.81, -0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.
接受I型干扰素治疗的多发性硬化症（MS）患者疾病活动度降低。由于免疫球蛋白（Igs）、补体和淋巴细胞在MS发病机制中发挥了作用，我们研究了α-2a干扰素（IFNA）对这些参数变异性的纵向影响。患者接受450万国际单位（MIU）IFNA治疗6个月（24例患者）、9.0 MIU IFNA治疗6个月（21例患者）或安慰剂治疗6个月（23例患者）。IFNA使总IgG以及IgG亚类1、3和4的浓度显著升高。在6个月时，9.0 MIU IFNA组的IgG平均浓度升高了1.51 g/l（可信区间：0.82，2.21）。IFNA治疗对IgG2和IgA的浓度无显著影响，而对IgM的影响接近显著。6个月后，9.0 MIU IFNA组的IgM升高了0.29 g/l（可信区间：-0.01，0.65）。IFNA使C1抑制剂（INH）的浓度显著升高。在3个月时，C1 INH的平均浓度升高了0.033 g/l（可信区间：0.01，0.05）。在3个月时，9.0 MIU IFNA组的C4升高了0.05 g/l（可信区间：0.01，0.09）。IFNA对C4的影响尚无定论，但表明在治疗初始阶段有作用。C3未显示出由治疗介导的显著变化。IFNA在3个月时使淋巴细胞浓度显著降低，降低了0.56×10⁶淋巴细胞/ml（可信区间：-0.81，-0.31）。免疫参数的变化与临床和磁共振成像评分的变化之间无显著关联。结果证实IFNA调节并激活了免疫系统的固有和适应性分支。这些观察结果在评估IFN治疗MS的作用机制时应具有相关性。
