Interleukin-10 regulation in normal subjects and patients with asthma
Interleukin-10 regulation in normal subjects and patients with asthma
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DOI：
10.1016/s0091-6749(96)70197-5
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发表时间：
1996-06-01
影响因子：
14.2
通讯作者：
Wenzel, S
中科院分区：
文献类型：
--
作者：
Borish, L;Aarons, A;Wenzel, S
白细胞介素-10或细胞因子合成抑制因子在免疫性疾病中具有重要的治疗作用。我们推测，哮喘中IL-10的产生减少将允许促炎细胞因子的不受阻碍的合成，从而促进哮喘的发展和严重程度。我们的数据表明IL-10在正常非哮喘受试者的支气管肺泡灌洗液（BAL）中的组成性分泌（130 +/- 61 pg/ml; n = 8）。哮喘患者的支气管肺泡灌洗液的特征是IL-10浓度降低（9 +/- 18 pg/ml; n = 8;与正常受试者相比p < 0.01）。通过使用基于RNA的聚合酶链反应，我们证明了减少的IL-10发生作为抑制转录的结果。IL-10的转录，但不是蛋白质，观察到在晚期哮喘反应的时间。我们推测IL-10蛋白的随后出现可能有助于晚期哮喘反应的解决。与在BAL液中观察到的相似，哮喘患者外周血单个核细胞表现出自发性减少，（0.01 +/- 0.01 ng/ml-哮喘和0.09 +/- 0.04 ng/ml-正常; p < 0.05）和刺激（0.60 +/- 0.22 ng/ml-哮喘和1.69 +/- 0.49 ng/ml-正常; p < 0.05）与正常受试者相比的IL-10产生。为了支持IL-10减轻炎症发展的假设，我们证明了向正常受试者的静息外周血单核细胞培养物中加入中和性抗IL-10抗体可刺激干扰素-γ的自发产生（10.4 +/- 4.3至152.4 +/- 23.6 ng/ml; p < 0.01）。最后，我们推断皮质类固醇可能通过诱导IL-10分泌发挥至少部分的抗肿瘤活性。然而，甲泼尼龙抑制了脂多糖刺激的IL-10的产生（单独使用脂多糖时IL-10为2.34 +/- 0.49 ng/ml，在另外存在10（-6）mol/L甲泼尼龙时为1.11 +/- 0.38 ng/ml; p < 0.05）。
Interleukin-10 or cytokine synthesis inhibitory factor has important antiinflammatory activities in immune diseases. We speculated that diminished IL-10 production in asthma would permit the unopposed synthesis of proinflammatory cytokines, contributing to the development and severity of asthma. Our data demonstrate constitutive secretion of IL-10 into bronchoalveolar lavage (BAL) fluid of normal nonasthmatic subjects (130 +/- 61 pg/ml; n = 8). Asthmatic patients' BAL fluid was characterized by diminished concentrations of IL-10 (9 +/- 18 pg/ml; n = 8; p < 0.01 compared with that of normal subjects). By using the RNA-based polymerase chain reaction, we demonstrated that diminished IL-10 occurred as a result of inhibition of transcription. IL-10 transcription, but not protein, was observed at the time of the late asthmatic response. We speculate that the subsequent appearance of IL-10 protein could contribute to the resolution of the late asthmatic response. Similar to what was observed in the BAL fluid peripheral blood mononuclear cells of patients with asthma demonstrated decreased spontaneous (0.01 +/- 0.01 ng/ml-asthmatic and 0.09 +/- 0.04 ng/ml-normal; p < 0.05) and stimulated (0.60 +/- 0.22 ng/ml-asthmatic and 1.69 +/- 0.49 ng/ml-normal; p < 0.05) IL-10 production compared with normal subjects. In support of the hypothesis that IL-10 mitigates the development of inflammation, we demonstrated that the addition of a neutralizing anti-IL-10 antibody to resting peripheral blood mononuclear cell cultures of normal subjects stimulated the spontaneous production of interferon-gamma (10.4 +/- 4.3 to 152.4 +/- 23.6 ng/ml; p < 0.01). Finally, we reasoned that corticosteroids might exert at least part of their antiinflammatory activity through the induction of IL-10 secretion. However, methylprednisolone inhibited the lipopolysaccharide-stimulated production of IL-10 (2.34 +/- 0.49 ng/ml IL-10 with lipopolysaccharide alone to 1.11 +/- 0.38 ng/ml in the additional presence of 10(-6) mol/L methylprednisolone; p < 0.05).