Iron and Fever

Warm-blooded animals have an elaborate physiological control system to maintain a constant body temperature. In man, this temperature is about 37°C. Any significant deviation from this temperature puts stress on the body and makes it difficult to maintain metabolic processes at their normal rates. Why then, during sickness, should the temperature rise? It would seem that development of fever would cause things to go from bad to worse, and make it more difficult for the body to recuperate. Fever is a complex and little understood phenomenon. Nevertheless, it is becoming more and more evident that fever can, in fact, be very beneficial to an organism. It is common practice today to make every effort to reduce fever during illness. It would not surprise me at all if in the future we are told to let a fever run its course because of its benefit to the recuperative processes. I would like to discuss one aspect of fever as it relates to iron metabolism and infectious disease.

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Although the protective value of fever during infection must certainly be very complicated, I would like to point out one aspect which is related to iron. In the course of his studies on microbial siderophore biosynthesis, Garibaldi made an interesting observation (Garibaldi, 1972). If the temperature of cultures was raised a few degrees above the normal growth temperature of 37 ° C, the organisms would survive quite well, but they ceased to produce siderophores. Garibaldi was the first to point out the possible medical significance of . this observation. Without iron, the bacteria cannot grow within the body. We have seen that during infection the body restricts the levels of blood plasma iron in order to make it more difficult for the microbes to grow. It may be possible that one of the reasons that fever is produced is to inhibit the ability of the microorganism to produce siderophores, which might otherwise effectively compete for the last traces of iron in the blood plasma. Thus, normal body temperature and adequate iron nutrition may be just fine for people in good health, but may actually be detrimental at the onset of infection.

Over 300 years ago, Sydenham said that "fever is a mighty engine which Nature brings into the world for the conquest of her enemies." Perhaps loss of appetite to restrict iron intake is one of the pistons of that engine. A popular old wives' tale is to "feed a cold but starve a fever." Fevers may be caused by bacterial infection, the infection being slowed by lack of iron. Colds are caused by viruses. Viruses do not contain iron.

Fever prevents bacteria from obtaining iron in the from the blood stream,