Ross C, Svenson M, Nielsen H, Lundsgaard C, Hansen M B, Bendtzen K
Laboratory of Clinical IFN Research, Institute for Inflammation Research, Rigshospitalet University Hospital, Copenhagen, Denmark.
Blood. 1997 Sep 15;90(6):2376-80.
High-avidity antibodies against interferon alpha (IFN alpha), interleukin-1alpha (IL-1alpha), and IL-6 have been demonstrated in preparations of normal human IgG, and in vivo modulation of these cytokines may therefore account for immunomodulatory and anti-inflammatory effects of high-dose intravenous IgG therapy. We have investigated the in vivo recovery and the effect on serum cytokine levels of antibodies to IFN alpha, IL-1alpha, and IL-6 infused with IgG preparations. Fifteen treatment series of 0.4 g IgG/kg/d were administered over 3 days to eight patients with autoimmune diseases. All IgG preparations contained variable amounts of antibodies binding to 125I-labeled human IFN alpha2A, -IL-1alpha, and -IL-6, and the contents of these molecules correlated with increased levels in serum anticytokine activities after IgG infusion. The infused anti-IL-1alpha antibody activity was fully recovered, whereas the recovery of anti-IFN alpha2A antibodies was significantly reduced. Serum antiviral activities were significantly reduced after IgG therapy (before, 0 to 5.6 IU/mL; after, 0 to 0.6 IU/mL). In contrast, enzyme-linked immunosorbent assay (ELISA) showed no significant reduction in the serum levels of IL-6 (before, 1 to 70 pg/mL; after, 2 to 55 pg/mL), and the levels of IL-1alpha were consistently below the detection limit (<30 pg/mL). In conclusion, increased levels of antibodies to IFN alpha2A, IL-1alpha, and IL-6 occurred in patients receiving IgG and this reduced the serum antiviral activity.
在正常人IgG制剂中已证实存在针对干扰素α（IFNα）、白细胞介素-1α（IL-1α）和IL-6的高亲和力抗体，因此这些细胞因子的体内调节可能解释了大剂量静脉注射IgG疗法的免疫调节和抗炎作用。我们研究了与IgG制剂一起输注的针对IFNα、IL-1α和IL-6的抗体在体内的恢复情况及其对血清细胞因子水平的影响。对8例自身免疫性疾病患者，在3天内给予15个疗程的0.4 g IgG/kg/d治疗。所有IgG制剂都含有不同量的与125I标记的人IFNα2A、-IL-1α和-IL-6结合的抗体，这些分子的含量与IgG输注后血清抗细胞因子活性的升高相关。输注的抗IL-1α抗体活性完全恢复，而抗IFNα2A抗体的恢复则显著降低。IgG治疗后血清抗病毒活性显著降低（治疗前为0至5.6 IU/mL；治疗后为0至0.6 IU/mL）。相比之下，酶联免疫吸附测定（ELISA）显示IL-6的血清水平没有显著降低（治疗前为1至70 pg/mL；治疗后为2至55 pg/mL），且IL-1α水平一直低于检测限（<30 pg/mL）。总之，接受IgG治疗的患者体内针对IFNα2A、IL-1α和IL-6的抗体水平升高，这降低了血清抗病毒活性。
