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Our foster-nurse of nature is repose.

William Shakespeare, King Lear (1605–6)

Some of the most interesting, least well understood, and potentially important consequences of sleep deprivation are found within the immune system. In short, lack of sleep can impair the body’s immune defences and thereby make us more susceptible to infection by bacteria, viruses and parasites.

The evidence comes mostly from research with other species. In one experiment, for example, mice that were immunised against the influenza virus were resistant to infection if they were exposed again to the virus a week later. But if the immunised mice were deprived of sleep for seven hours immediately after being exposed to the virus, they were no more resistant to infection than mice that had not been immunised at all. A mere seven hours of sleep deprivation disturbed their immune response enough to erase the benefits of immunisation.

Some scientists have suggested that one reason why prolonged sleep deprivation is ultimately fatal is that it breaks down the animal’s immune defences, making it vulnerable to infection by any opportunistic bacteria and viruses that happen to be in the vicinity. Experiments with rats have shown that following severe sleep deprivation, the lymph nodes and other organs are invaded by potentially dangerous bacteria, which appear to have migrated there from the intestines. However, the role of infection in killing sleep-deprived animals remains a controversial issue.

Sleep loss impairs the human immune system as well. Even modest sleep deprivation evokes measurable changes. One night of sleep loss lowers the activity of natural killer cells and reduces the numbers of several different types of white blood cells circulating in the bloodstream. (Natural killer cells are a special type of lymphocyte, or white blood cell, that attack virus-infected cells and certain types of cancer cells.) Depriving healthy adults of sleep for seven hours on one night suppressed their natural killer-cell activity by 28 per cent. It bounced back to normal after a night of uninterrupted sleep. Moderate sleep loss will also reduce the body’s production of interleukin-2, a chemical messenger substance that plays an important role in regulating immune responses. After two or three days of sleep deprivation there is a marked decline in the responsiveness of lymphocytes and an even bigger fall in the activity of natural killer cells.

Sleep loss might play a role in the well-established connection between severe depression and impaired immune function. Depressed people generally sleep badly and have poorer immune responses. The more disrupted their sleep, the bigger the decline in their immune function. One study, for example, found that people who were suffering from depression following bereavement had fewer natural killer cells. The bereaved subjects were troubled by intrusive thoughts that often woke them or kept them awake during the night. The extent of the reduction in their natural killer-cell numbers was correlated with the amount of time they spent awake during the night: the more troubled someone was by their loss, the more disrupted their sleep and the fewer natural killer cells circulating in their blood. Sleep deprivation could be one of the mechanisms by which depression makes people more vulnerable to illness.

The relationship between sleep and immunity works in both directions. Not only does sleep affect the immune system, but the immune system also affects sleep. The immune reactions triggered by infection and illness can elicit alterations in sleep patterns. That is why infections are often accompanied by lethargy, loss of appetite, depressed mood and general malaise. Animals infected with influenza virus display a large increase in sleep about 24 hours after exposure to the virus. These changes in wakefulness are part of the body’s defence mechanisms and assist the recovery process. Human experiments, in which noble volunteers were injected with bacterial toxins, found that sleep is highly sensitive to the activation of the immune defences. Low-level infection tends to promote deep sleep. However, a full-blown infection accompanied by fever induces lethargy but typically disrupts sleep. You might have noticed that you sleep more deeply for a night or two when your body is fending off a potential infection, whereas when you are in the throes of a galloping illness you feel exhausted but lie for hours without sleeping.

The immune response to infection stimulates the release of chemical messenger substances that act on the brain to induce malaise, drowsiness, loss of appetite and sleep. During infection, a substance known as interleukin-1 stimulates the brain to induce deep sleep, while other interleukins trigger the fever that often accompanies infections. They do this by adjusting the brain’s temperature control centres – in effect, putting the body’s thermostat on a higher setting. That is why we feel hot and sleepy when we have a bad infection. The fever response is a defence mechanism found in all animals: the rise in body temperature makes life harder for the offending bacteria or viruses, and the lethargy forces the infected organism to curl up in a dark corner and sleep until it has recovered. It all makes good biological sense.

The brain and the immune system are interconnected through an elaborate network of chemical and neural communication channels. One important link between sleep, immune function and psychological stress is the steroid hormone cortisol. Sleep deprivation and prolonged stress both provoke an increase in the level of cortisol. After one night of sleep loss, your cortisol levels would typically be raised by about 45 per cent the next evening. It is not good to have elevated cortisol levels for too long, since cortisol has a powerful suppressive effect on the immune system. The functioning of the immune system is also intimately bound up with the 24-hour sleep – wake cycle and the circadian rhythms in hormone levels. Various aspects of immune function fluctuate in tune with the circadian cycle. Anything that disrupts the normal cycle of sleep and wakefulness therefore tends to disturb the immune system, with potential consequences for the body’s ability to defend itself against infection and disease.

The intimate relationship between sleep and immune function takes on a potentially huge practical significance when you consider how widespread sleep deprivation has become in society. Tired people are more likely to become sick people.