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The Effects of Fasting and Refeeding on Regulating NLRP3 Inflammasome Activation in Asthmatic Subjects
Author(s) -
Nguyen An,
Li Jessica,
KwartengSiaw Miriam,
Traba Javier,
Han Kim,
Sack Michael
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb737
Subject(s) - inflammasome , medicine , asthma , endocrinology , peripheral blood mononuclear cell , meal , inflammation , biology , biochemistry , in vitro
The NLRP3 inflammasome is linked to inflammatory diseases including asthma. Interestingly, we have shown that fasting (24 hours) blunts and refeeding (3 hours after a meal) activates the NLRP3 inflammasome in peripheral blood mononuclear cells (PBMCs) from normal volunteers and that the serum extracted at the fasted and refed time points can recapitulate this effect in THP‐1 macrophage cells. At the same time it has also been found that intermittent fasting reduces asthma exacerbations in a clinical study. Based on this we have begun to evaluate whether fasting and refeeding regulate the NLRP3 inflammasome in mild to moderate asthmatic subjects exposed to a 24 hour fasting and 2.5 hour refeeding protocol. Preliminary studies in the first 8 study participants have been analyzed. Interestingly, the asthma subjects (n=3) who were not treated with inhaled steroids showed a 24% increase in refeeding activation of the NLRP3 inflammasome as measured by IL‐1β release as was found in the normal volunteers. However, the asthma subjects (n=5) who were treated with inhaled corticosteroids did not show an induction of the inflammasome with refeeding (rather a 39% reproduction in IL‐1β release compared to fasting). When comparing the serum from the asthmatic subjects, the results were opposite to the normal controls where serum from fasting subjects showed increased IL‐1β release in response to inflammasome triggering compared to serum from the fed state. Interestingly, the baseline IL‐1β levels were markedly elevated in the asthmatic subjects serum compared to the normal controls. These preliminary data suggest that: (i) inhaled steroids have systemic effects and disrupt the immune modulatory effects of fasting and refeeding; (ii) the basal inflammatory milieu evident in asthma disrupts the nutrient‐deprivation effect on blunting the NLRP3 inflammasome. Support or Funding Information Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD USA.Biomedical Research Training Program for Individuals from Underrepresented Groups (BRTPUG), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD USA.