Adaptive Value of Fever

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It has been difficult to obtain data pertinent to the question of whether fever has a beneficial or harmful effect on an infected host. As the result of indirect evidence, it has often been assumed that fever has survival value. This is because fever is an energetically costly process. As a febrile organism elevates its body temperature, it consumes considerably more energy, simply as the result of the effects of temperature on biochemical or metabolic processes. This has led to the conclusion that this process would not have evolved had it no adaptive function.

What about hard experimental data? Conceptually, one way to resolve whether fever is adaptive would be to infect a group of mammals with some harmful bacteria or virus and then allow one half to develop a normal fever and prevent the other half from raising their body temperatures. The survival of the two populations of mammals would be compared and if fever were harmful, then the group which was prevented from elevating its body temperature would have a greater survival rate. If fever were beneficial, then the opposite results would be obtained. The problem with this experiment is that it is very difficult to attentuate the fever in an infected group of mammals without making the results difficult to interprete. In the process of preventing the fever, one must administer antipyretic drugs or perform some other manipulation which would confound the results. For example, would the differences in the survival rate of the two populations be attributable to the effects of the drugs on body temperature or to some side effect not related to their antipyretic properties? There have, nevertheless, been many experiments, using mammals, which have attempted to resolve whether fever is adaptive or maladaptive, and while the results of these studies are difficult to interpret, they tend to indicate that in many cases fever is beneficial to the infected host.

Another approach to determining the function of fever has been to find a more appropriate animal to use in one’s investigations. This really becomes a question of selecting the best animal to use to answer a specific question. For example, if one is interested in the effects of some drug on the cardiovascular system, then one often uses the dog or the laboratory rabbit as the experimental animal. One advantage is that they are large and, therefore, relatively easy to work with. Another and perhaps more important advantage is that since their cardiovascular system is similar to that of human beings, the results obtained using these animals can often be extrapolated to other vertebrates, including man. Neurobiology is another area in which the proper selection of an experimental animal has produced important results. When one is interested in some aspect of nerve cell function, cells from invertebrates, such as the squid, are often used. These cells are often selected because they are large and easily accessible. Furthermore, since the physiology of nerve cells tends to be relatively conservative from one group of animals to another, the results obtained using the nerve cells of most invertebrates can be extrapolated to basic nerve processes in other groups of organisms. The scientific literature is literally filled with the fruitful results obtained by investigators who carefully selected the most appropriate animal species for their investigations.

It seemed to us that one way to resolve the question of the role of fever in disease would be to use an ectothermic organism as the experimental animal. An ectotherm (in contrast to an endotherm) is an organism which regulates its body temperature largely by behavioral processes. Reptiles, amphibians, and fishes are examples of ectothermic vertebrates. If these organisms developed fevers in response to infection, then one would have an excellent experimental animal to use to investigate fever’s function. Such an animal could be infected with live pathogenic organisms, and because its body temperature could be easily controlled by the experimenter, it would be possible to investigate the effects of holding the animal at febrile and afebrile body temperatures.

First, we had to determine whether ectotherms developed fevers in response to infection. If they did, this by itself would provide indirect evidence that fever was beneficial, for why else would fever be found in vertebrates from fishes through mammals? As a result, a series of experiments was initiated to trace the evolution of fever. Much of this book is a summary of these investigations, by members of my laboratory and others, to trace the evolution and to investigate the adaptive value of fever.

This entry was posted on Tuesday, July 21st, 2009 at 9:22 am and is filed under physiology. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

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