Cortisol, Suppressed Immune Function, and Cancer
We know that during periods of increased stress, there is often also an increase in the incidence of certain chronic conditions such as asthma, allergies, and rheumatoid arthritis, as well as of gastrointestinal ailments such as irritable bowel syndrome (IBS) and Crohn's disease. This is quite interesting, because each of these conditions is considered to have an autoimmune component to it—meaning that one's own immune system has gone a bit haywire and has started to attack one's own tissues. In these cases, doctors often prescribe synthetic versions of cortisol as a way to suppress an overactive immune system, and it works quite well—but only for a short period of time. The problem with using synthetic cortisol as a medication, however, is that too much of the stuff, or even a modest amount for too long, leads to the very same tissue breakdown and metabolic disturbances that occur when experiencing chronic stress.
Medical researchers have known for more than sixty years that chronic or repeated bouts of stress will lead to a shrinking of the thymus gland (one of the key immune tissues in the body) and to a general suppression of immune-system strength. We know that cortisol has a direct effect on shrinking the thymus and inhibiting white blood cell production and activity. Cortisol suppresses the ability of white blood cells to secrete chemical messengers (interleukins and interferons), so the different varieties of immune-system cells become unable to communicate with each other in a way that would allow them to more effectively fight off infections. Finally, and most remarkably, is the fact that cortisol can actually act as a signal to many immune-system cells to simply shut off and stop working (that is, the cells die).
Now, why would stress and cortisol have all of these detrimental effects on the immune system? You would think that during times of stress, the body would want to increase its resistance to invading pathogens (bacteria and viruses) rather than decrease this vital protection—but this is clearly not what happens. To answer this question we need to again consider the timing of the stress response. Just as the relationship between cortisol and appetite has an aspect of timing to it (stress suppresses appetite for a few seconds or minutes, but then stimulates appetite for the next few hours), the relationship between cortisol and immune-system function is also mediated by timing. If we look at stress/immunity in these terms, we see that immune function is actually stimulated by stress for a short period of time (a few minutes). This short blast of immune-system stimulation appears to be used by the body to "wake up" existing immune-system cells as well as to "clear out" cells that fail to work properly due to normal cell aging.
This is all very good: Now you have a short-term stressor that has ramped up immune-system activity and you're ready to fight off the invading bugs. The problem, as it has been for many of the bodily systems discussed thus far, is that a prolonged stress response sends these finely regulated systems into complete chaos. During periods of chronic stress, cortisol levels remain elevated and immune-system integrity begins to suffer. Not only do the chronically stimulated immune-system cells start to break down, losing their ability to fight off invading pathogens, but in some cases they can start to unleash their destructive properties on the body's own tissues, resulting in a variety of allergies, as well as in autoimmune diseases such as multiple sclerosis, lupus, fibromyalgia, and rheumatoid arthritis.
Confused yet? If not, then you should be, because most of the world's top immunologists and stress physiologists are baffled by the fact that stress increases immune-system function on the one hand, but then turns around and dismantles one of our most important protective systems on the other. One of the proposed reasons for this "Jekyll and Hyde" effect of cortisol has to do with the fact that while a stimulated immune system is good on a short-term basis, undergoing this stimulation on a long-term basis may actually lead to autoimmune diseases (wherein the immune system attacks the body's own tissues).
It makes good sense for cortisol to stimulate immune-system activity during stress, and when cortisol levels return to normal (after the stress is over) for overall immune-system activity to normalize as well. Unfortunately, our modern high-stress lifestyles (the Type C condition) don't allow cortisol levels to return to normal. Consequently, one of the body's "safety valves" comes into play, whereby chronic exposure to cortisol causes the immune-system cells to break down, thus preventing autoimmune diseases, but also reducing our ability to ward off future infections and increasing our risk for many diseases.
Speaking of autoimmune diseases, it is important to make the point (again) that glucocorticoids (of which cortisol is one) are routinely used by physicians to combat autoimmune diseases. If we think of autoimmune diseases as conditions wherein an overactive immune system attacks our joints (rheumatoid arthritis) or nerve cells (multiple sclerosis) or connective tissue (lupus), then it is logical to knock down this overzealous immune system with a huge dose of cortisol (glucocorticoids). In this way, cortisol can be thought of as our "friend" by suppressing immune-system activity, but cortisol can also be thought of as our "enemy" because of the memory problems, muscle loss, and other side effects experienced by patients injected with high doses of glucocorticoids. Unfortunately, during times of stress these very same autoimmune diseases tend to flare up—which is confusing, because the stress-induced rise in cortisol would be expected to reduce immune-system activity and actually help control the diseases. Again, it probably comes down to timing, with short-term stress causing a temporary stimulation of immune activity and, thus, an increase in the symptoms of the autoimmune condition.
Studies in both animals and humans have noted a reduction by as much as 50 percent in levels of immune-system cells called natural killer cells following exposure to various forms of stress. Natural killer cells (NK cells) typically function within the immune system to identify viruses and cancer cells. In one study of breast cancer patients, the level of emotional stress caused by the initial cancer diagnosis was directly related to NK cell activity. In these women, a higher stress level predicted a reduced ability of NK cells to destroy cancer cells as well as a poorer response to interventions aimed at improving NK cell activity. From animal studies, we know that cortisol not only suppresses the number and activity of NK cells, but also promotes the synthesis of new blood vessels in tumors (a process called angiogenesis) and accelerates the growth of certain kinds of tumors. The bottom line here may be that chronic stress can accelerate the growth of cancer cells in the body as well as block the body's ability to battle the disease.
Heightened stress levels have also been linked to adverse effects on the balance of intestinal microflora, which are known to respond to changes in both diet and stress level. These beneficial bacteria live in our intestinal tract, and while they are intimately involved with optimal gastrointestinal function (more on this later), they also play a vital role in helping to support immune function. In a study of fighter pilots preparing for simulated battle (a fairly stressful event), distinct reductions were noted in the numbers of "good" bacteria (lactobacilli and bifidobacteria), along with a corresponding increase in the numbers of "bad" bacteria (E. coli, enterobacteria, and clostridia). The outcome for these pilots was, predictably, a sharp increase in their reported incidence of sore throats, headaches, colds, diarrhea, and upset stomachs.
In some stress-management clinics, the primary determinants of whether or not a given person will get sick include:
- the number of major life events in the past year (divorce, death in the family, change in job or location, etc.)
- a psychological perception that daily demands exceed coping resources and/or support system
- current emotional state
Of this short list of three "sickness determinants," researchers have found that the overall degree of psychological stress is strongly related, in a dose-response fashion, to URTIs (upper-respiratory-tract infections) and other breakdowns in immune-system integrity (such as gastrointestinal health). This means the more stressed out you are, the more likely you are to get sick.
Numerous studies in animals and humans have shown that both acute and chronic stress increases susceptibility to infectious diseases. In particular, the risk of upper-respiratory-tract infections (URTIs) is sharply increased, so that people who are under the greatest stress (or who deal with it poorly) are the ones who most often get these types of sicknesses. Students catch colds during exam week, and accountants get sore throats in April, when they're filing dozens of last-minute tax returns.
Swedish researchers have found chronic stress to increase the occurrence of yeast infections, a consequence likely due to the overall suppression of immune-system activity caused by the stress. Brazilian researchers have linked elevated stress to both depression and suppressed immune function, and they have suggested that chronic stress may contribute to the development of certain forms of cancer. In a series of experiments, results show that various cellular and molecular aspects of the immune system are impaired in patients suffering from chronic stress and depression, yielding, for example, high levels of cortisol and inflammatory cytokines, and reduced numbers and activity of T cells and NK cells, the specific immune-cell types responsible for the immune system's surveillance of cancer tumors.
We have known for many years that some forms of cancer are related to increased levels of psychological stress. Researchers from the University of Wisconsin Medical School have recently shown that breast cancer patients have a flattened cortisol rhythm (resulting in an elevated twenty-four-hour exposure to cortisol) that predicts a shorter survival time.
So after all this discussion about the suppression of immune-system function due to stress, who do you think gets sick most often? What demographic group, among all others, suffers from the highest incidence of stress-related disease?
- Wealthy investment bankers? No.
- Stressed-out college students? No.
- Single mothers working two jobs and driving beat-up 1985 Ford Escorts? Yes!
The most direct example of the chronically elevated human stress response can be observed every day in the lives of a large part of the American (and worldwide) population. These are the folks who are driving a junker car (and hoping it makes it) to their second job. They are hoping the money from that second paycheck will last until the end of the month when the bills are due. They are not the people whom you see commiserating with each other about their terrible jobs on sitcoms such as Friends. The constant unrelenting stress of making ends meet, job instability, sleep deprivation, poor diet, lack of outlets for stress, and overall lack of control combine to increase the risk of disease by a factor of five to ten!
Unfortunately, none of the information or recommendations that follow in this book will alleviate the actual stressors encountered by the "working poor" or by the "working middle class" (wherever you choose to draw the economic line)—but much of what follows can be used to reduce the damage wreaked by stress on all of us.