Effect of Fasting and Refeeding on T-cell Fate
Condition: Asthma; Inflammation
MeSH terms: Inflammation
Study type: Observational

Summary: 
      Background:

      Researchers want to better understand the body s immune response to calorie restriction. To
      do this, they are asking healthy volunteers to fast for 24 hours. Researchers will test
      immune response before and after fasting.

      Objectives:

      To explore the benefits of calorie restriction on immune health.

      Eligibility:

      Healthy volunteers ages 21 to 37 with a body mass index between 22 and 29.

      Design:

      Participants will be screened with medical history, physical exam, and blood tests.

      Participants will visit NIH after an overnight fast. Their baseline immune response will be
      taken. They will give blood and urine samples. Then they will be given breakfast. This visit
      will take about 2 hours.

      Participants will fast (not eat or drink anything except water) for the next 24 hours. They
      will return to NIH the next morning. Their immune response will be taken. They will give
      blood and urine samples. Then they will be given breakfast. Their immune response will be
      taken 3 hours later. They will give a blood sample. This visit will take about 4 hours.
    

Detailed description: 
      Intermittent caloric restricted or fasting has numerous health effects including the
      reduction in numerous cardiovascular and pulmonary disease risk factors. The cellular
      programs activated by caloric restriction are similarly regulated in preclinical and clinical
      studies in response to a 24-hour fast. We have found that a beneficial effect of a 24-hour
      fasting blunts the activation of a component of the innate immune system, termed the NLRP3
      inflammasome. This inflammasome, as a mediator of sterile inflammation, is associated with
      the development of diabetes, asthma and atherosclerosis. At the same time, we found that
      refeeding after the 24-hour fast significantly increased NLRP3 protein levels. As NLRP3 is
      increased in obesity, the nutrient intervention (24 hour fast and then refeeding) we studied
      may be useful to evaluate nutrient-overload effects on the immune system. Pertaining to this
      it has recently been found in a preclinical study that NLRP3 can also orchestrate
      differentiation of na(SqrRoot) ve T cells into T(H)2 cells. Interestingly both the NLRP3
      inflammasome and T(H)2 cell activation contribute to asthma. In this context we hypothesize
      that the assessment of the effect on refeeding on T(H)2 cell differentiation (polarity) may
      allow us to dissect out the mechanisms underpinning nutrient overload induced T(H)2 cell
      activation. To evaluate this blood samples to test T-cell biology will be collected in
      subjects, at baseline, after a fixed caloric meal and in response to a 24-hour fast (water
      intake will not be restricted). The objective of this pilot study is to identify if
      nutrient-load regulates T-Cell differentiation capacity and to test whether this pathway
      could be investigated as a therapeutic target to blunt/negate the inflammation associated
      with nutrient-excess associated diseases including asthma.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        -Males and females between the ages of 21 and 37 @@@-BMI greater than or equal to 22 and
        less than 30
      
Keywords: NLRP3 Inflammasome; Sirtuin 3; T-Cell Polarity; Caloric Restriction; Natural History