Interleukin-4 receptor in moderate atopic asthma - A phase I/II randomized, placebo-controlled trial
Interleukin-4 receptor in moderate atopic asthma - A phase I/II randomized, placebo-controlled trial
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DOI：
10.1164/ajrccm.160.6.9808146
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发表时间：
1999-12-01
影响因子：
24.7
通讯作者：
Garrison, L
中科院分区：
文献类型：
--
作者：
Borish, LC;Nelson, HS;Garrison, L
白细胞介素 - 4在哮喘中具有重要的促炎作用，包括诱导IgE同种型转换、内皮细胞上血管细胞黏附分子 - 1（VCAM - 1）的表达、黏蛋白产生、15 - 脂氧合酶活性以及刺激Th2淋巴细胞导致白细胞介素 - 4、白细胞介素 - 5和白细胞介素 - 13的二次合成。可溶性重组人白细胞介素 - 4受体（IL - 4R；Nuvance； altrakincept）可使天然存在的白细胞介素 - 4失活，而不介导细胞活化。雾化的白细胞介素 - 4受体血清半衰期约为1周。在这项双盲、安慰剂对照试验中，25名需要吸入糖皮质激素的中度哮喘患者在停止吸入糖皮质激素后，被随机分配接受单次雾化剂量为1500μg、500μg的白细胞介素 - 4受体或安慰剂。未观察到与药物相关的毒性。白细胞介素 - 4受体治疗在第4天使第一秒用力呼气容积（FEV1）显著改善（1500μg对比安慰剂；p < 0.05），在第2天和第4天使用力呼气流量（25% - 75%肺活量）（FEF25 - 75）显著改善（1500μg对比安慰剂；p < 0.05）。尽管突然停用糖皮质激素，但接受1500μg白细胞介素 - 4受体治疗的患者哮喘症状评分稳定，而500μg白细胞介素 - 4受体组或安慰剂组则不然（p < 0.05）。1500μg白细胞介素 - 4受体组的患者使用β₂ - 激动剂进行急救的需求也显著减少（p < 0.05）。呼出一氧化氮显著减少进一步证明了其抗炎作用（p < 0.05）。结论：单剂量白细胞介素 - 4受体在中度哮喘中似乎是安全有效的。1500μg剂量似乎与500μg剂量同样安全，但明显更有效。
Interleukin-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, expression of VCAM-1 on endothelium, mucin production, 15-lipoxygenase activity, and Th2 lymphocyte stimulation leading to the secondary synthesis of IL-4, IL-5, and IL-13. Soluble recombinant human IL-4 receptor (IL-4R; Nuvance; altrakincept) inactivates naturally occurring IL-4 without mediating cellular activation. Nebulized IL-4R has a serum half-life of approximately 1 wk. In this double-blind, placebo-controlled trial, 25 patients with moderate asthma requiring inhaled corticosteroids were randomly assigned to receive a single nebulized dose of IL-4R 1,500 mu g, IL-4R 500 mu g, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV1 on Day 4 (1,500 mu g versus placebo; p < 0.05) and in FEF25-75 on Days 2 and 4 (1,500 mu g versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1,500 mu g, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 mu g group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 mu g group also required significantly less beta(2)-agonist rescue use (p < 0.05). Anti-inflammatory effects were further demonstrated by significantly reduced exhaled nitric oxide (p < 0.05). Conclusions: A single dose of IL-4R appears safe and effective in moderate asthma. The 1,500 mu g dose appears as safe but significantly more effective than the 500 mu g dose.