Influence of Lifestyle Factors on Neutrophil Migration Pilot Study
Condition: Neutrophil Chemotactic Response
Study type: Interventional

Summary: 
      This study will determine how common lifestyle practices affect the behavior of neutrophils
      (a type of immune cell) at shorter time scales than previously possible.
    

Detailed description: 
      This study will investigate how external factors implicated in immunity such as exercise,
      caffeine ingestion, ethanol, glucose, and glucose and caffeine ingestion influence neutrophil
      migration.

      Neutrophils are the most prominent immune cell in human blood and are involved in a complex
      equilibrium of immune protection and autoimmune damage. Their recruitment to an inflammatory
      or wounding site is controlled by the sensing and directed migration to a concentration
      gradient of attractant molecules, a process called chemotaxis. Immune cells are also
      implicated in many diseases including cancer. The ability to measure the amplitude of a
      response over time for a specific patient, and the variation of this response when the
      patient engages in certain activities or consumes certain substances will improve
      understanding of how certain lifestyle factors impact the immune response. Traditional assays
      require large volumes of blood and a long purification process, which may affect neutrophil
      function and strictly limits the number of draws possible from a single patient. The novel
      microfluidic assay proposed limits these drawbacks as it has the capability to purify
      neutrophils from a 3 µL drop of blood in less than 5 minutes and measure their chemotaxis in
      a gradient of chemokines. Critically, the proposed studies will begin to fill a gap in
      current understanding of immune response as previous studies focused on single endpoints
      likely missing early events in the response to external stimulus. Understanding this temporal
      response may have implications in the development of new treatments as well as improvements
      in diagnosis of improper immune response.

      The KOALA (Kit On A Lid Assay) approach was developed in Professor Dave Beebe's lab and has
      been validated in a mouse model and in human asthmatic patients. In a collaboration with Dr.
      Anna Huttenlocher, it has been shown that, in contrast to traditional neutrophil
      purification, KOALA can be performed with small volumes of blood, and a much quicker
      purification time.

      Due to its unique qualities, KOALA allows for repeated evaluation of neutrophil adhesion and
      chemotaxis properties, thus making it an attractive method for studying dynamic neutrophil
      changes that may occur as a result of an external factor.

      Using traditional macrobiology tools, researchers have identified several factors that may
      play important roles in reducing neutrophil responsiveness and migration ability. Lifestyle
      and diet factors, amongst others, have been shown to impact neutrophil count, migration and
      biochemical function. For example, sleep deprivation has been linked with higher neutrophil
      count, despite a known immuno-depressive effect. Physical exercise results in increased
      neutrophil counts and increased neutrophil degranulation. Dietary factors, such as caffeine
      and ethanol have been shown to impact immune function.

      Blood glucose will be tested at each time point using a blood glucose monitor to determine
      whether the lifestyle factor is affecting blood glucose (and consequently, neutrophil
      function). Alcohol consumption can cause both high and low blood sugar. Specifically, while
      low doses of alcohol may have a protective effect against risk of diabetes and metabolic
      syndrome, heavy drinking has been associated with higher glucose levels, resulting in
      increased risk of both diabetes and metabolic syndrome. Similarly, acute ingestion of
      caffeine has been shown to increase blood glucose levels, but several epidemiological studies
      have shown regular coffee consumption in associated with a lower risk of type 2 diabetes.
      Measuring blood glucose on subjects in the glucose study may show dose dependent effects on
      neutrophils.

      To build on this research, the investigators intend to probe the role of these lifestyle
      factors on neutrophil migration over much shorter time scales than has been previously
      studied. The investigators propose to examine the effects of exercise, ethanol ingestion and
      caffeine consumption on neutrophil behavior.

      Whole blood obtained from subjects by finger stick will be used in KOALA to isolate
      neutrophils. Neutrophil function will be assessed by measuring absolute migration speed,
      chemotactic index and chemotaxis velocity (directional velocity toward the formation of the
      gradient of chemoattractant).

      The primary outcome of this study will be to determine whether exercise, caffeine
      consumption, ethanol, glucose and combined glucose and caffeine ingestion affect neutrophil
      chemotactic velocity. The secondary outcomes are to determine whether exercise, caffeine
      consumption, ethanol, glucose and combined glucose and caffeine ingestion affect the absolute
      speed and chemotactic index of neutrophils. The investigators will also assess whether
      cytokine profiles in the blood change as a result of engaging int he specified lifestyle
      factors.
    

Intervention name(s): Exercise; ProLab 200mg caffeine capsule; Ethanol ingestion; Glucose Tolerance Drink
Intervention type(s): Behavioral; Drug; Other; Drug
Intervention description(s): Participants will ride a stationary bike and maintain their target heart rate (according to the American Heart Association guidelines) for 30 minutes.; Participants will swallow one ProLab caffeine 200mg tablet.; Participants will consume a dose of 80 proof alcohol according to their body weight to reach a breath alcohol concentration of 0.05.; Participants will consume 100 grams of glucose
Intervention MeSH terms: Ethanol; Caffeine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science