Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and.
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 2018 Sep 1;201(5):1382-1388. doi: 10.4049/jimmunol.1800585. Epub 2018 Jul 18.
A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production and reduced CD4 T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.
禁食模拟饮食可减轻炎症，间歇性禁食已显示出对肥胖哮喘患者的改善作用。为了研究与哮喘相关的经典炎症途径是否受禁食调节，我们在轻度哮喘患者中设计了一项试点研究，以评估禁食对 NLRP3 炎性小体、Th2 细胞活化和气道上皮细胞细胞因子产生的影响。招募了有记录的可逆转气道阻塞和稳定的轻度哮喘患者参加这项研究，在禁食后 24 小时进行肺功能测试（PFT）和 PBMC 提取，并在重新进食后 2.5 小时重复进行 PFT 测试和采血。长时间禁食不会改变 PFT。然而，皮质类固醇初治的轻度哮喘患者表现出 NLRP3 炎性小体的禁食依赖性减弱。此外，与重新进食的样本相比，这些禁食的哮喘患者的 PBMC 与人上皮细胞共培养导致屋尘螨诱导的上皮细胞细胞因子产生减少和 CD4 T 细胞 Th2 活化减弱。这项初步研究表明，长时间禁食可减弱皮质类固醇初治哮喘患者的 NLRP3 炎性小体和 Th2 细胞活化，并减少气道上皮细胞细胞因子的产生。这确定了营养水平依赖性炎症调节在哮喘中的潜在作用。我们的研究结果支持在更大规模的研究中评估这一概念，以及开发热量限制干预措施治疗哮喘的潜力。
