Oh, I feel bad…
Why do we feel lousy when we get sick?
Together with the Alpina non-fiction publishing house, PostNauka publishes an excerpt of Robert Sapolsky's book "Testosterone Games and Other issues of behavior biology", which tells about the main components of the human biological foundation.
Recently, I had a huge number of vaccinations – I was preparing to go to the tropics. Then, while I was trying to get comfortable on my pricked ass, the nurse explained that vaccines – especially the typhus vaccine–can lead to a slight malaise. And indeed, by the evening I felt lousy.
It was especially unpleasant because I wasn't really sick. And I didn't have to be afraid that I had malaria, flu or the plague. I knew what the reason was, and I knew it wasn't serious. In fact, vaccines work because they make the body believe that it is slightly ill and it is time to defend itself. We are usually not aware of the ongoing staging of the battle, but some vaccines – including typhus – have particularly strong effects. So I couldn't really feel sorry for myself, I knew I'd be fine by morning. It was a solid form without content – I felt sick, although I was not sick.
A lousy state of health is caused by a wide variety of diseases. I want to sleep all day. Joints ache, chills hit. Sexual desire disappears. Appetite disappears; if the disease progresses, we lose weight, even if we cram food into ourselves. And the patient looks like a sucker. Not so long ago, Benjamin Hart, a veterinarian at the University of California, Davis, compiled a list of 60-something diseases common in mammals that cause the same set of symptoms, although they affect different organs. Infect a person with influenza affecting the respiratory system; infect a cat with infectious anemia affecting the blood, infect a sheep with enterotoxemia affecting the intestines – and everyone will complain of pain, whine and want to get under the covers in pajamas.
From a medical point of view, such symptoms traditionally do not arouse interest. Suppose you have the flu and you complain to the doctor about weakness and joint pain. I bet the most common answer would be, "Of course you are weakened. Of course, your joints hurt. After all, you are sick!" These symptoms are so nonspecific and ubiquitous that they don't seem to count. But in recent years, scientists have learned a lot of interesting things about where bad health comes from when we suffer from infectious diseases. Symptoms do not arise by themselves – the body tries to cause them, and it seems that it has serious reasons for that.
At the center of this story is the immune system and the white blood cells that it uses to fight the disease. When a pathogen – an infection like a virus or a bacterium – enters the body, the immune system is the first to sound the alarm: a large utilizer cell, called a macrophage, immediately grabs the pest. The macrophage, in turn, transmits the infectious agent to the T helper cell, which signals that the cheeky stranger really deserves concern. Then the macrophage starts a chain of events, which ends with the activation of T-killers attacking the pest. This chain is called cellular immunity.
Meanwhile, the second form of protection, known as humoral immunity, is triggered: T-helpers introduce another type of white blood cells – B-lymphocytes into play, stimulating their division and differentiation; as a result, they begin to produce antibodies for the aggressor that will grab and immobilize him.
Immunologists have been dealing with these processes for decades. They found out that the immune response involves a number of cell types throughout the body. To communicate with distant cells, the immune system uses cytokines – chemical signaling molecules that travel in the bloodstream and lymph. That's where the poor state of health comes on the scene.
Among the most well–known signaling molecules are interferons, which activate white blood cells that fight viruses and cancer, and interleukins, which are necessary to start a chain of T cells. The most interesting interleukin is called IL-1 (interleukin-1), its main job is to transmit an alarm signal from the macrophage (where this signal is formed) to T cells. But we get sick because that's not all: IL-1 also acts on the brain.
The most noticeable thing that this interleukin does is to change the temperature regulation. It has long been known that after infection, the immune system secretes something that causes fever. No one knew what exactly, and the alleged source was called an endogenous pyrogen (if there are pyromaniacs and borosilicate glass manufacturers in the ranks of readers, then the meaning of this term is obvious to them). But that this pyrogen was IL-1 was determined only in the early 1980s.
In our brain there is a special area called the hypothalamus, which works on the principle of a thermostat. Normally, it is set at 36.6 degrees. If the body temperature drops below, a tremor begins to generate heat, blood is diverted from the periphery of the body to important organs and you want to get under a pile of blankets. The temperature above 36.6 turns on sweating, quickens breathing to quickly waste heat. And IL-1 shifts the reference point of the thermostat higher. In other words, at 36.6 you get cold and warming reactions are triggered: a new equilibrium is achieved at a higher temperature. You have a fever.
But that's not the only way IL-1 makes you feel lousy. A few years ago, two groups of scientists (mine and the European one) simultaneously reported that IL-1 also causes the hypothalamus to secrete a substance called corticotropin-releasing hormone, or KRG. This substance controls the hormonal response of the body to stress, triggering a chain of signals from the hypothalamus to the pituitary gland, and from there to the adrenal glands, which prepare you for an emergency.
Imagine that you go into a store, and suddenly a rhinoceros rushes after you with the clear intention of tearing you to pieces. At the same second, you will start to stand out KRG, and for good reason. The corticotropin release factor blocks energy storage, purposefully inhibiting the processes by which the body stores fat in the form of triglycerides and sugar in the form of glycogen. Energy is instead hastily redirected to the muscles that carry you away, past the shelves with products. At the same time, KRG reduces appetite, sexual desire and reproductive processes. These are logical actions: it is not very reasonable at such a moment to waste energy on ovulation or planning lunch.
Approximately the same thing happens when infected. Interleukin-1 triggers the release of KRG, and soon food and sex lose their appeal. Sex hormone levels are plummeting, and if the disease lasts long enough, ovulation and sperm formation may be suppressed.
There are other symptoms of poor health that can be blamed on interleukin-1. It causes drowsiness – although no one knows how. And he does something else especially nasty.
From different parts of the body – from the surface of the skin, and from the depths of the muscles and ligaments – there are nerve pathways that transmit pain signals to the spinal cord. These signals are transmitted to the brain, which interprets them as painful. Stepping on a nail is certainly a painful incentive: the nerve pathway starting in the toe is activated, and the brain registers pain at the same moment. But stimuli of lower intensity do not overcome the threshold of activation of the neural pathway. They will not be perceived as pain unless the threshold is lowered. This is exactly what IL-1 aims at: it makes the neurons of this pathway more excitable, prone to respond to stimuli that normally they would ignore. Your joints suddenly begin to ache, old injuries ache, your eyes become inflamed.
All together, it makes up an impressive set of consequences of the activity of a substance that was considered just a carrier of signals in the immune system. And precisely because of this, interleukins are not very suitable for medicines: theoretically, they could help fight the disease by stimulating the immune system. But from such treatment you are guaranteed to get sick. Cancer patients who were given IL-2 (a close relative of IL-1) felt disgusting.
Biologists have figured out a little bit about exactly how IL-1 causes symptoms of ill health. It binds to receptors on the surface of neurons involved in pain perception, temperature regulation and the release of CRH. In turn, this triggers the synthesis of prostaglandins – intracellular compounds that signal the need to change the reference point of temperature and sensitivity to pain. So, theoretically, it is possible to reduce many of the symptoms of poor health if you take a medicine that blocks prostaglandin synthesis. Which is what aspirin does.
Another important aspect of the disease syndrome needs to be explained: cachexia, or weight loss. It is obvious that with a long-term illness, weight is lost, given what is happening with appetite. But cachexia is something more. With a chronic illness, you lose weight faster than could be explained by a reduction in nutrition. The body fails to store energy.
About the author:
Robert Sapolsky – professor of Neurology and Neurosurgery at Stanford University.
Portal "Eternal youth" http://vechnayamolodost.ru