Thermoregulatory Control, Fever, and Behavioral Fever

Of all the physiological control systems, the system for thermoregulation is the one that usually seems the most straightforward conceptually. Virtually every introductory treatment of control theory in physiology uses the thermoregulatory control system as its central example. This is undoubtedly true because analogies can so readily be drawn with engineered thermal control systems, which are common in our everyday lives.

In a house with a furnace and air conditioner, the thermostat controls heat production by the furnace and heat removal by the air conditioner to maintain a stable air temperature. Using the terminology of control theory to describe this system, the air temperature is the controlled variable (see Box 1.1), and the furnace and air conditioner are effectors, instruments that are capable of changing the controlled variable. The thermostat itself actually includes three separate elements that are essential for a control system:

1. A sensor, a device that can measure the controlled variable so that the control system knows its current level (the current air temperature).
2. A set point or reference signal. The set point is a type of information that remains constant in a control system even as the controlled variable goes up and down, and that tells the system the desired level of the controlled variable. We usually call the set point of a home thermostat its “setting.” If, for example, we “set” the thermostat to 20°C, the device is able to retain that set-point information in an invariant form, so that the air temperature detected by the sensor can be compared with it. An important point to recognize is that a thermostat does not remember its set point by having inside it an object that is kept literally at the set-point temperature. Instead, the set-point temperature is represented in the thermostat by a physical system that is not a temperature, but corresponds to a temperature.
3. A controller, a mechanism that compares the set point with the current level of the controlled variable to decide whether the controlled variable is too high or low.

The control system in a house, considered as a whole, operates as a negative feedback system (see Box 1.1). It controls the effectors to bring the controlled variable back toward the set point. For example, if the air temperature goes below the set point, the furnace is commanded to add heat to the house.

By analogy, it is easy to describe the thermoregulatory control system of a lizard or mammal (or any other thermoregulator) in terms of the same basic concepts. The principal effectors in a lizard (a behavioral thermoregulator) are the skeletal muscles that move the limbs and control posture. Effectors in a mammal include muscle cells that can produce heat by shivering, sweat glands that can promote evaporative cooling, hair-erector muscles that determine how fluffed the pelage is, and so forth. A lizard or mammal has multiple sensors: temperature-sensitive neurons that measure the current temperatures of the skin, spinal cord, and brain. These sensors send their temperature data to a controller in the brain that compares the current temperatures with a set point to decide what to do. The exact natures of the controller and set point remain far from fully understood because they consist of many tiny neurons in the depths of the brain. As in the case of the home thermostat, however, we recognize that the set point is not literally a temperature in the brain but is represented in some way by neurons.

If we disregard the uncertainties that exist about the nature of the set point and simply use the terminology of control theory, the set point of a lizard or mammal can be adjusted to different “settings” at different times, just as the setting of a home thermostat can be adjusted. Fever in a mammal provides an elegant example of resetting of the thermostat (see the figure). Fish, amphibians, and nonavian reptiles sometimes develop fevers—called behavioral fevers because the effectors are skeletal muscles that modify behaviors. In Box Extension 10.3 we discuss thermoregulatory control and especially fever in more detail.

A bout of fever in a placental mammal: The relation between the set point of the thermoregulatory control system and body temperature When the set point jumps up at the start of a bout of fever and falls back down at the end, the thermoregulatory control system detects the mismatch between the set point and the body temperature and commands vigorous effector responses to correct the mismatches. These responses include shivering at the start and sweating at the end.

The effectors employed in thermoregulation by a behavioral thermoregulator, such as a lizard, are different from the effectors employed by mammals and birds. If a lizard’s body temperature is too low and the lizard’s controller receives information from sensors that the tissues are too cool, the lizard’s controller commands behaviors that move the lizard to a warmer place. If a mammal’s body temperature is too low, the mammal’s controller might activate shivering and command fluffing of the pelage.

In a classic fever, people go through alternating periods of shivering and sweating, a pattern that reflects changes in the thermoregulatory set point. At the start of a bout of fever, as the figure shows, a person’s set point is raised. A difference between the body temperature and the set point is created by this rise in the set point. The controller detects this difference and issues commands that activate effectors that will correct the difference. Shivering, restriction of cutaneous blood flow, and other processes thus occur and raise the person’s body temperature to the new set point. Later, when the set point falls back to normal, a difference between the body temperature and the set point is again created by a change in the set point. Again, the controller detects this difference and issues commands that activate effectors that will correct it. Sweating, flushing of the skin with blood, and other processes then occur that bring the person’s body temperature to the lowered set point. The rise of the set point during fever results from a series of events set in motion by the presence in the body of molecules termed pyrogens. The best-known pyrogens are lipopolysaccharides in bacterial cell walls.

One of the most remarkable discoveries in thermal biology in the twentieth century was that lizards, other nonavian reptiles, amphibians, and fish sometimes develop fevers. When these animals are infected with certain sorts of bacteria, their set points go up, and they move to warmer environments where they have higher body temperatures! This sort of fever, as already mentioned, is called behavioral fever. There are many reasons to believe that such behavioral fevers in poikilothermic vertebrates are homologous to physiological fevers in mammals. Thus the presence of fever in poikilothermic vertebrates is an intriguing type of evidence that there is evolutionary continuity between the thermoregulatory control systems in poikilothermic and homeothermic vertebrates.

Researchers have capitalized on the phenomenon of behavioral fever to investigate the significance of fever for disease. Because a lizard or other poikilotherm can be prevented from developing fever merely by being kept in a cool place, investigators have been able to carry out experiments that directly compare animals that develop fevers with ones that do not. Individual poikilotherms prevented from behaviorally elevating their body temperatures when infected with bacteria often suffer greater morbidity and mortality than do individuals of the same species that are allowed to develop fevers. Such results suggest that fever evolved as a defense against disease.

Copyright 2016 Sinauer Associates