Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response
Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response
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DOI：
10.1016/s0140-6736(00)03497-8
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发表时间：
2000-12-23
期刊：
影响因子：
168.9
通讯作者：
Barnes, PJ
中科院分区：
文献类型：
--
作者：
Bryan, SA;O'Connor, BJ;Barnes, PJ
背景白细胞介素-12（IL-12）是一种巨噬细胞衍生的细胞因子，可调节T淋巴细胞反应，并具有抑制过敏性和嗜酸性粒细胞炎症的能力。25、0.5 μ g/kg（n=19）或安慰剂（n=20）。我们比较了第一次注射前24小时和最后一次注射后24小时对吸入性过敏原激发的反应。结果IL-12导致第四次注射后24小时与安慰剂相比，主要外周血嗜酸性粒细胞计数较基线显著降低（p=0 . 001）。0001）。与安慰剂相比，用IL-12治疗时，在变应原激发后24小时，痰嗜酸性粒细胞也显著减少（p=0 . 001）。024）。IL-12导致气道对组胺的高反应性改善的非显著趋势，但对吸入过敏原激发后的晚期哮喘反应没有显著影响。IL-12给药后，19例患者中有4例过早退出; 2例心律失常，1例肝功能异常，1例患者有严重的流感样症状。Interpretation我们已经表明IL-12降低了血液和痰嗜酸性粒细胞的数量，但对气道高反应性或哮喘反应没有任何显着影响。这对嗜酸性粒细胞在介导这些反应中的作用提出了质疑，并对开发新的抗炎治疗方法具有重要意义。
Background interleukin-12 (IL-12) is a macrophage-derived cytokine that modulates T lymphocyte responses and has the capacity to suppress allergic and eosinophilic inflammation.Methods We carried out a double-blind, randomised, parallel group clinical study, in which patients with mild allergic asthma were given subcutaneous recombinant human IL-12 at increasing weekly injections of 0 .1, 0 . 25, 0 .5 mug/kg (n=19), or placebo (n=20). We compared responses to inhaled allergen challenge 24 h before the first injection and 24 h after the final injection. Airways hyper-responsiveness and concentrations of peripheral blood eosinophils and sputum eosinophils were also assessed.Findings IL-12 caused a significant decrease from baseline in the main peripheral brood eosinophil count 24 h after the fourth injection compared with placebo (p=0 . 0001). Sputum eosinophils were also significantly decreased 24 h after allergen challenge when treated with IL-12 compared with placebo (p=0 . 024). IL-12 caused a non-significant trend towards improvement in airway hyper-responsiveness to histamine, but had no significant effect on the late asthmatic reaction after inhaled allergen challenge. After administration of IL-12, four of 19 patients withdrew prematurely; two with cardiac arrhythmias, one with abnormal liver function, and a single patient with severe flu-like symptoms.Interpretation We have shown that IL-12 lowers numbers of blood and sputum eosinophils, but without any significant effects on airway hyper-responsiveness or the tate asthmatic reaction. This questions the role of eosinophils in mediating these reactions, and has important implications for development of new anti-inflammatory treatments.