Why during sickness should body temperature of warm-blooded animal rise? It has long been known that the level of serum iron in animals falls during infection. Garibaldi first suggested a relationship between fever and iron. He found that microbial synthesis of siderophores – substances that bind iron – in bacteria of the genus Salmonella declined at environmental temperatures above 37℃ and stopped at 40.3℃. Thus, fever would make it more difficult for an infecting bacterium to acquire iron and thus to multiply. Cold-blooded animals were used to test this hypothesis. Kluger reported that of iguanas infected with the potentially lethal bacterium A. hydrophilia, more survived at temperatures of 42℃ than at 37℃, even though healthy animals prefer the lower temperature. When animals at 42℃ were injected with an iron solution, however, mortality rates increased significantly.