Lawrence Steinman is professor of neurology and pediatrics at Stanford University in California.
The concept of a sentry is reassuring. In earlier times, a sentry was posted outside a town's gates to guard against enemies. Today, they're posted around military bases in combat zones. Our body has its own elaborate sentry system, with fever as the early-warning system to report emerging danger from harmful viruses and bacteria. We have all experienced fever and some of the usual symptoms accompanying that rise in body temperature, including shivering and sweating, fatigue, weakness, muscle pain and loss of appetite.
Screening for Ebola at ports of entry is being undertaken in Canada, Britain and the United States. At certain airports in Canada – Montreal, Toronto, Vancouver, Halifax, Ottawa and Calgary – as well as in key U.S. airports, screening of passengers follows protocols set up by national health authorities. In the U.S., officials monitor the body temperature of passengers arriving from countries where the Ebola epidemic rages. Passengers running a fever may be subject to quarantine as this fever is one of the earliest warning signs of an Ebola infection. Fever is also a clue that the communicable phase of the virus has begun, that the passenger can now spread the infection.
Although we are all undoubtedly familiar with the experience of fever, our understanding of its physiology represents a triumph of medical science. Over the past century, physicians and scientists have unravelled the intricate interplay between our immune systems and a particular centre in our brains that mediates the rise in body temperature known as fever; this brain region, the size of an almond, is called the hypothalamus.
Fever ensues when our immune system responds to the danger signals contained in viruses and bacteria. The chemistry of some of these signals has been established. Many of our immune cells, known as white blood cells, have a specific receptor that is activated by the mere presence of a small molecular signal warning of infection. This signal triggers a rapid response, allowing the white blood cells to attack the foreign invader. Ebola virus contains particles that stimulate these receptors – named "toll-like receptors" – on our white blood cells.
When these receptors on immune cells are engaged, the immune cell is then activated to release molecules called pyrogens. A pyrogen is a term that literally means an inducer of fever. The first pyrogen that was discovered is known as interleukin-1. These interleukins promote communication between the white blood cells of the immune system and distant structures like those in the brain. Pyrogens travel in the blood stream to the hypothalamus.
In the hypothalamus, within the brain, the pyrogens activate a biochemical cascade involving another fatty chemical called prostaglandin. The cascade leads to the production of prostaglandin E2 (PGE2). The cascade can be interrupted by drugs like Aspirin, which work to reduce fever.
PGE2 activates the temperature sensing cells in the brain, called thermosensitive neurons. These cells govern our molecular thermostat, and when exposed to PGE2 the thermostat is set at a higher body temperature. These neurons are located close to others in the hypothalamus that control appetite and sleep.
The outcome of this process in the hypothalamus results in the familiar rise in body temperature that we know as fever, sometimes accompanied by a paradoxical shaking chill, and then a feeling of sleepiness and loss of appetite. The shared location of these brain cells within the hypothalamus accounts for why we see a familiar constellation of these symptoms with the rise in temperature in fever.
Elevated temperature remains the most dependable and the earliest warning sign of communicable infection with Ebola. Of course other infections can also trigger fever, so when one monitors for the presence of fever, not all will have Ebola. However, it is quite practical to measure fever – a sentry with an infra-red scanning thermometer can stand at an airport entrance and determine whether a given passenger has elevated temperature, and is thus at risk for transmitting Ebola.
Fever has been featured in the movies, in literature and in popular music. In Ferris Bueller's Day Off, Ferris feigns something like it to miss a day of school. In Sonnet 147, William Shakespeare wrote, "My love is as a fever." Fever was a memorable R&B song that first hit the charts in 1956. But alongside this upbeat notoriety, fever is certainly more than just a key concept for scripts, lyrics and poetry. We all know it, having suffered with it during an infection, and this familiarity apparently attracts our attention.
The remarkable chemistry and wiring between our immune systems and our brains have provided not only a cleverly constructed early warning system for our personal defence, but in the case of Ebola, also a warning system for a first line of national defence.