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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 where pulmonary function testing (PFT) and peripheral blood mononuclear cells (PBMCs) extraction was performed 24 hours after fasting, with repeated PFT-testing and blood draw 2.5 hours after refeeding. PFT’s were not changed by a prolonged fast. However, steroid-naïve mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics co-cultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production, and reduced CD4+ T cell Th2 activation compared to refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naïve 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.