That's a good point, Gigalos and thanks for pointing it out. There are a number of channels through which chronic stress depresses your immunity. The following summary is from Stanford scientist Robert Sapolsky's brilliant book,
Why Zebras Don't Get Ulcers:
How Does Stress Inhibit Immune Function?
It’s been almost sixty years since Selye discovered the first evidence of stress-induced immunosuppression, noting that immune tissues like the thymus gland atrophied among rats subjected to nonspecific unpleasantness. Scientists have learned more about the subtleties of the immune system since then, and it turns out that a period of stress will disrupt a wide variety of immune functions.
Stress will suppress the formation of new lymphocytes and their release into the circulation, and shorten the time preexisting lymphocytes stay in the circulation. It will inhibit the manufacturing of new antibodies in response to an infectious agent, and disrupt communication among lymphocytes through the release of relevant messengers. And it will inhibit the innate immune response, suppressing inflammation. All sorts of stressors do this— physical, psychological, in primates, rats, birds, even in fish. And, of course, in humans, too.
The best-documented way in which such immune suppression occurs is via glucocorticoids. Glucocorticoids, for example, can cause shrinking of the thymus gland; this is such a reliable effect that in olden days (circa 1960), before it was possible to measure directly the amount of glucocorticoids in the bloodstream, one indirect way of doing so was to see how much the thymus gland in an animal had shrunk. The smaller the thymus, the more glucocorticoids in the circulation. Glucocorticoids halt the formation of new lymphocytes in the thymus, and most of the thymic tissue is made up of these new cells, ready to be secreted into the bloodstream. Because glucocorticoids inhibit the release of messengers like interleukins and interferons, they also make circulating lymphocytes less responsive to an infectious alarm. Glucocorticoids, moreover, cause lymphocytes to be yanked out of the circulation and stuck back in storage in immune tissues. Most of these glucocorticoid effects are against T cells, rather than B cells, meaning that cell-mediated immunity is more disrupted than antibody-mediated immunity. And most impressively, glucocorticoids can actually kill lymphocytes. This taps into one of the hottest topics in medicine, which is the field of “programmed cell death.” * Cells are programmed to commit suicide sometimes. For example, if a cell begins to become cancerous, there is a suicide pathway that gets activated to kill the cell before it starts dividing out of control; a few types of cancers involve the failure of the programmed cell death to occur. It turns out that glucocorticoids can trigger those suicide pathways into action in lymphocytes, through a variety of mechanisms.
Sympathetic nervous system hormones, beta-endorphin, and CRH within the brain also play a role in suppressing immunity during stress. The precise mechanisms by which this happens are nowhere near as well understood as with glucocorticoid-induced immune suppression, and these other hormones have traditionally been viewed as less important than the glucocorticoid part of the story. However, a number of experiments have shown that stressors can suppress immunity independently of glucocorticoid secretion, strongly implicating these other routes.
But then there is the question of why. Why would the body suppress it's own immune response?
Well, he can explain that better than I can. The first reason would be related to the whole "Fight/Flight" vs. "Rest/Digest" duality that I referred to in the hypothesis in my last post. Basically, when you are stressed out and hyped up, it's time to fight and you don't have time to rest and digest.
But what if, when you are fighting, you skin your knee? You need your immune response, as you mentioned. Why is the body doing this? Sapolsky writes, "Various ideas have floated around over the years to explain why you actively disassemble immunity during stress with the willing cooperation of the immune system. Some seemed fairly plausible until people learned a bit more about immunity and could rule them out. Others were quite nutty, and I happily advocated a few of these in the first edition of this book. But in the last decade, an answer has emerged, and it really turns this field on its head."
Well, it turns out that it is actually just chronic stress that decreases immunity. The short term stress response actually boosts it, according to Sapolsky. (Of course, all of this is so complex and nuanced that it is hard to make generalizations like this, but let's use this as a starting point.) However, if the immunity is boosted for too long, there is an increased chance of autoimmune diseases, so after the immune response has been running for a while, it begins to suppress the increased immune system that it, itself, started. And if you keep the stress up for too long, it can even drive them down below their normal levels. He writes, "For most things that you can measure in the immune system, sustained major stressors drive the numbers down to 40 to 70 percent below baseline." As a result, you start seeing things like stressed out people getting frequent colds or flareups in chronic infections.
Anyway, that's his story in the third edition of the book. It corresponds to the major theme of his book that chronic stress can cause chronic illnesses because we were designed for the short term stress that our caveman ancestors would have faced. This is Sapolsky's answer to the question that forms the title of the book. Q:
Why do Zebras Not get Ulcers? A: Because they are still in their natural environment. Our bodies, like their bodies, were designed for short term stresses, not chronic stresses, so the chronic stresses of modern life can take a devastating toll over the course of a long life.
By the way, unlike Sapolsky, I don't have three full professorships at Stanford, and I'm afraid I need to take back what I wrote about epinephrine causing a decrease in inflammation. The companion stress chemical, cortisone, definitely does this, but it is not clear that the epinephrine is what cuts the inflammation. In the abstract, the authors write, "In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia
resulting in profoundly increased plasma epinephrine levels.
In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group.
In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases."
In other words, there was a correlation between the epinephrine and the subsequent suppression of the immune response. However, causality was not established.
So does epinephrine suppress inflammation? According to the
information provided by the makers of epipen, during anaphylaxis, epinephrine works through its impact on α- and β-adrenergic receptors. The effect on β2-receptors includes decreased release of inflammatory mediators (including histamine and tryptase). This would suggest that there may be a channel through which epinephrine can suppress inflammation. However, we should not conclude that this pathway necessarily explains the phenomena in the paper.
As a result of looking more at the above I read more about epinephrine and anaphylaxis, and my thoughts there are different as well. My current understanding is that while inflammation is tied up in the allergic reaction of anaphylaxis, adrenalin/epinephrine isn't used to treat anaphlaxis because it decreases the inflammation or components of the allergic reaction, but rather because it counteracts them. For example, blood vessels get larger in anaphylaxis, decreasing blood pressure. Epinephrine counteracts this by causing blood vessels to contract. Similarly, epinephrine can open up the air passages in our lungs, perhaps because our body "thinks" (evolutionarily speaking) we need more air for fight or flight during the stress response.
Dr. Sarno was very proud of his affiliation with NYU and with medical science, and thinking more about all of this has reminded me of how important it is to take careful guidance from people who, like Dr. Sarno, have spent decades studying the biology of mindbody medicine.
I thought I'd close with a couple of other quotes from this chapter of Sapolsky's excellent book:
- The evidence for the brain’s influence on the immune system goes back at least a century, dating to the first demonstration that if you waved an artificial rose in front of someone who is highly allergic to roses (and who didn’t know it was a fake), they’d get an allergic response.
- In 1982 the report of an experiment using a variant of this paradigm, carried out by two pioneers in this field, Robert Ader and Nicholas Cohen of the University of Rochester, stunned scientists. The two researchers experimented with a strain of mice that spontaneously develop disease because of overactivity of their immune systems. Normally, the disease is controlled by treating the mice with an immunosuppressive drug. Ader and Cohen showed that by using their conditioning techniques, they could substitute the conditioned stimulus for the actual drug— and sufficiently alter immunity in these animals to extend their life spans.
