Durelli L, Bongioanni M R, Cavallo R, Ferrero B, Ferri R, Verdun E, Bradac G B, Riva A, Geuna M, Bergamini L
Clinica delle Malattie del Sistema Nervoso, Università di Torino, Italy.
Mult Scler. 1995;1 Suppl 1:S32-7.
Interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-alpha counteracts many of the proinflammatory actions of IFN-gamma and TNF-alpha. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-alpha-2a (rIFN-alpha) (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rIFN-alpha-treated and in 7/8 placebo-treated patients (P < 0.005). Only one new MRI lesion was detected in the rIFN-alpha group, while 27 new or enlarging lesions were detected in placebo group (P < 0.01). Baseline lymphocyte IFN-gamma (19.10 +/- 7.12 U ml-1) and TNF-alpha (18.05 +/- 5.34 pg ml-1) production significantly decreased to 3.03 +/- 0.66 (P < 0.04) (for IFN-gamma) and to 5.78 +/- 0.90 (P < 0.04) (for TNF-alpha) after rIFN-alpha treatment. IFN-gamma and TNF-alpha production was unchanged in the placebo group. rIFN-alpha was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-alpha might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.
干扰素γ（IFN-γ）和肿瘤坏死因子α（TNF-α）是促炎细胞因子，可能参与了多发性硬化症（MS）的发病机制。干扰素α可抵消IFN-γ和TNF-α的许多促炎作用。我们对20例复发缓解型（RR）MS患者进行治疗，其中12例患者每隔一天肌肉注射9百万国际单位（MIU）的重组干扰素α-2a（rIFN-α），共治疗6个月；另外8例患者注射安慰剂。接受rIFN-α治疗的12例患者中有2例出现临床病情加重或在系列磁共振成像（MRI）检查中发现新的或扩大的病灶，而接受安慰剂治疗的8例患者中有7例出现上述情况（P<0.005）。rIFN-α组仅检测到1个新的MRI病灶，而安慰剂组检测到27个新的或扩大的病灶（P<0.01）。基线时淋巴细胞产生的IFN-γ（19.10±7.12 U/ml）和TNF-α（18.05±5.34 pg/ml）在rIFN-α治疗后显著下降至3.03±0.66（P<0.04）（IFN-γ）和5.78±0.90（P<0.04）（TNF-α）。安慰剂组中IFN-γ和TNF-α的产生没有变化。rIFN-α耐受性良好，没有患者退出研究或出现严重副作用，但发热、不适、疲劳（两名患者的日常活动受到影响）和白细胞减少症经常发生。高剂量慢性全身性rIFN-α可能会减轻RRMS患者疾病活动的临床和MRI表现。细胞因子产生的变化表明，这种作用可能是由促炎细胞因子的下调介导的。
