Being sick isn’t fun. Whether it’s an eight-hour case of the sniffles or this year’s strain of the flu, nobody wants to deal with the fever, the achy joints, or the lack of energy. You don’t want to do anything but lay on the couch and ride out your misery.
While it’s easy to blame these feelings on the bug, you might be surprised at how much is your brain’s own doing.
Robert Dantzer of the University of Illinois studies the rather complex subject of psychoneuroimmunology (PNI).49 Fortunately P N I is easier to understand than to say in one breath.
As biologists have come to understand that living organisms are woven into complex nonlinear networks, it makes little sense to treat organ systems as separate, independent units. All the pieces integrate into the whole.
The mind, once treated as a spooky and immaterial x-factor, can be seen as interchangeable with the behavior of the brain, making mental health an important part of physical well-being.
In that spirit, the immune system and the nervous system overlap in so many ways that it’s difficult to draw a line between the two. The brain’s hormonal and neural messages stimulate the immune system into activity, and meanwhile the immune system’s own messengers relay information back to the brain.
Thus we have P N I, the intersection of psychology, neurology, and immunology. Mind is brain is immune response, and it makes little sense to speak of their function in separate terms.
When you get sick, even elementary school biology teaches that the immune system kicks in to fight off whatever bug has invaded your body. You’ve heard the story about how the white blood cells act as sentries, roving our bodies for troublemakers and shooting antibodies at invading microbes before digesting them.
The circulating immune system, including those T-cell and B-cell lymphocytes, is another evolutionary newcomer. The immune system has a much older set of defenses, found even in insects, meant to handle damage and infection at a local level. An infected cut, or a second-degree burn, or a twisted ankle will all turn red, swell up, and get hot to varying degrees, a process called inflammation.
That’s the innate immune system at work. Unlike the circulating white cells, the innate response happens in the damaged tissue itself, using a first-aid kit of growth factors, specialized clean-up cells, and inflammatory signals called cytokines. When you get that burn or twist your ankle during a run, all that machinery kicks in and starts running damage control.
Cytokines really set off the process. Almost every cell in your body is capable of producing them in response to trauma, broadcasting a signal that says “hey, something’s wrong here!” and bringing backup in the form of macrophages and other clean-up cells.
When the problem stays small, just a cut or mild burn, you won’t notice much else.
The area might stay tender for a few days, but it heals soon enough and that’s the end of it. In cases of more severe trauma or infection, however, it’s not so simple, and the inflammation process can itself become lethal in extreme instances.
Think what it’s like when you catch a nasty cold. You feel warm all over, more sensitive to pain, maybe stiff and sore, and you’re so tired you don’t want to get off the couch. Regardless of what kind of bug you catch, you always experience the same set of symptoms. Even though a case of the flu might leave you in bed, it’s still the same symptoms, only worse.
Inflammation-signaling cytokines not only attract immune cells for clean-up duty, but they also act on the brain through various channels. Those signals tell the brain that some major fighting and clean-up is going on, so the brain responds with a coping strategy. It wants you to stop moving and wasting energy so it can use those resources for recuperation, and to make that happen it triggers that set of physical symptoms. Dantzer calls this sickness behavior.
“Coping strategy” should ring a bell. Cytokines work on the hypothalamus, which you’ll recall as being involved in the stress-response, and as you might expect from that, sickness behavior evokes roughly the same set of stress-coping responses.
That isn’t too surprising if you think about it. “Squat flu” and similar terms are often used to describe how we feel the day after a beating in the gym, and for good reason:
those sensations work through the same mechanisms.
What’s more, that mechanism holds some unsettling connections with the biology of depression. Serotonin, a neurotransmitters which you’ll recall as having a role in central fatigue, works in parts of the brain responsible for, among other things, mood and the formation of memories. When serotonin transmission is low, you feel down in the dumps and can have trouble learning and remembering, and this state-of-being is thought to have a connection with major depression, anxiety disorders, and other assorted emotional problems.
Brain scans show that the majorly depressed have marked differences in the size of these serotonin-using regions compared to healthy people, leading some psychologists to hypothesize that the chronically-elevated glucocorticoids under prolonged stress can actually prune back the serotonin neurons. This leads to higher anxiety, deeper depression and, perversely, even higher corticoid levels, kicking off a self-sustaining death-spiral.
The similarities between “squat flu” and depression run deep. The inability to trigger voluntary movement is a pronounced symptom of depression. Patients literally cannot summon the will to move, a condition that mirrors the (admittedly less-pronounced) loss of motivation in both the sick and the overtrained. This is probably not a coincidence; I think it’s likely that all three work through similar (through probably not identical) mechanisms.50
Exercise scientist Lucille Smith first suggested the connection between the immune response and overtraining symptoms back in the 1990s. Smith found that elevated levels of a cytokine called interleukin 1-beta (IL-1b) correlated with “feeling bad” symptoms of tissue-damaging exercise. It was later discovered that IL-1b acts directly on the brain, not only signaling inflammation in muscles and other tissues, but activating sickness behavior.51
When you feel sore, achy, warm in the day or two after a hard workout, that’s the immune system telling you that you’re coping with the stress, what Smith called the cytokine hypothesis of overtraining. The overtraining symptoms experienced by athletes really are like being sick.
As with earlier “mental” phenomena associated with fatigue, the problem is not limited to your mood. Research is finding that the sickness state can, like other forms of stress, directly trigger muscle atrophy by activating the HPA. I’ll spoil the surprise: it’s IL-1b again. Inflammation signals the brain, signaling the H PA to increase glucocorticoid levels, and that triggers the catabolic atrophy effect in muscle tissue.
Now, most everyone you’ll talk to in the fitness industry will get mad and shake a fist at poor cortisol, but notice that the inflammatory cytokine, and the overall state of being inflamed and sick, is the real culprit here. Catabolic states are coordinated in the brain, and signaled by the immune system’s response. If you want to blame something, blame the brain. The hormone is just doing its job.52
What we have here is a reasonable explanation. Lots of exercise – especially unaccustomed exercise – triggers the inflammation response in your muscles and connective tissues, leading to mood-altering changes in your brain state as well as elevation of stress hormones. High volumes of tissue-damaging exercise can, like infections and trauma, trigger a feeling almost like a mild form of depression.