In my lab we look at stress and a great indicator of stress
is cortisol, a corticosteroid. Cortisol is involved in the
hypothalamic-pituitary-adrenal (HPA) axis. Cortisol follows a diurnal pattern
where there is a spike in cortisol between 20-45 minutes after awakening
followed by a steady decline in concentration during the day. Stressors, care
giving for loved ones going through an allogeneic bone marrow transplant is
what we use in our lab, can have an affect on the “typical” pattern and result
in shunting of the spike or no detectable decline in cortisol concentration
throughout the day. We take saliva samples throughout the day for three
consecutive days to get an idea of how stressed their body is.
With knowing how stressed a caregiver is we are comparing
cytokine levels with those of non-stressed subjects. We first suppress their
blood samples by adding different concentrations of Dexamethasone, an
immunosuppressant. This is done to suppress any immune response that was
occurring in the body before drawing the blood. After a half hour incubation we
then add lipopolysaccharide (LPS) to the whole blood, dexamethasone mixture and
let incubate for 24 hours. LPS is an endotoxin that binds to Toll-like receptor
4 of white blood cells. This initiates signaling cascades of cytokines. If
stress does suppress immune function then we would expect to see minimal
cytokine levels in the plasma as compared to non-stressed subjects. The main
question we want to answer is “does stress effect immune function and the
bodies ability to combat infection?”
If stress is found to have an effect on how well the immune
system function the next step is to figure out how to treat it. The easy answer
would be to remove the stress in that person’s life, but as in our study the
stress is caring for a loved one going through life threatening illness, you
can’t exactly remove that. Do we go the pharmacology route and try and boost
immune function? Or do we go with biofeedback systems that help the person calm
through breathing exercises and other noninvasive remedies?
Hmmm I think it would be best to first start with the pharmacology route. If someone is stressed and then gets sick due to a compromised immune system, then that won't help him/her get any better. However, once the immune system is healthy again, then they could switch over to the biofeedback systems like exercising and controlled breathing.
ReplyDeleteBecause if a person is stressed and tries to deal with that on their own, then they may get sick in the process which could add to their stress level and worsen the problem.
Sam7630,
ReplyDeleteFascinating post on the use of cortisol measurements to determine stress level in caregivers. I'm a student in the College of Nursing and there are a couple of researchers there who are using cortisol levels to measure sleep habits in both cancer survivors and their caregivers. They're using the saliva cortisol level to determine changes to the diurnal pattern, but to my knowledge aren't adding the steroid to the mix then measuring the response to the endotoxin.
How long does it take to stimulate a measurable innate immune response by targeting TLR-4? Which cytokines would that then produce? This is all new to me and it is fascinating to see it in action!
Thanks for the great post.
Michaela
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ReplyDeleteGreat post! I always enjoy hearing about what other people are involved with in research.
ReplyDeleteComparing stressed participants with controls, so far have you seen a difference in cytokine production between the groups in quantity? Also, I realize you expect to see that "if stress does suppress immune function then we would expect to see minimal cytokine levels in the plasma as compared to non-stressed subjects," but do you think that you might see a difference not in the amount of cytokine production, but in the cytokines produced instead?
It might be interesting if cytokines produced are involved in some sort of a negative feedback loop where some factor, i.e. stress, changes. The change is detected by a sensor which sends a message to an integrating center which in turn stimulates an effector to change something about the initial factor.
Furthermore, I wonder if looking at cytokine levels in WBC's at various time points might render a different cascade of cytokines produced. I am thinking that it is possible for some to spike early on to seeing LPS, and some later on.
Just some thoughts, interesting field of research. :)
I think stress does affect our immune system. There are lots of study done on the relationship between psychological stress effects on pro-inflammatory cytokine production and has effect on our body abilities to fight the infection.
ReplyDeleteI also think it would be best try both pharmacology route and biofeedback system at same time. While the medicine will be doing its job to relieve stress, at same time biofeedback system like controlling breathing and exercise will help more to feel relax and better. It will help calm our physiological arousal and might help to reverse the stress response.