Urinary excretion of zinc and iron following injection of bacteria in the unanesthetized rabbit.

The effects of injection of bacteria (Pasteurella multocida) on the urinary excretion of zinc and iron (during the period when plasma concentrations of these trace metals were falling) were determined in unanesthetized New Zealand white rabbits. During the initial 2 h following injection with bacteria there was a trend towards an increased urinary excretion of zinc and iron. This short-term increase in zinc and iron excretion, however, could only account for a small percentage of the reduction in plasma concentrations of these trace metals that occurs during infection. We conclude that most of the reduction in plasma iron and zinc that occurs during infection is attributable to a redistribution within the body and not to increased excretion.

Endogenous cryogen excreted by the kidneys.

Injection (iv) of human urine into rabbits results in a fall in body temperature accompanied by peripheral vasodilation in a thermoneutral ambient temperature and suppression of shivering metabolism in the cold. There were no consistent changes in mean arterial pressure in response to the injection of urine. If the production of urine is prevented by occlusion of the ureters of rabbits, body temperature falls. Injection of endogenous pyrogen (iv) into rabbits, which have had their ureters occluded, results in a significant attenuation in the magnitude of the fever as compared to controls. These observations suggest that there is an endogenously produced cryogenic substance ("endogenous cryogen") normally excreted in an active form by the kidneys and which when either injected, or prevented from being excreted (by clamping the ureters), results in a regulated fall in body temperature. In addition, in human patients on regular dialysis treatment who still had residual renal function, the oral temperature was slightly below normal before hemodialysis and slightly above normal after hemodialysis, a difference averaging 0.39 degrees C (P less than 0.001). These data are in agreement with the hypothesis that endogenous cryogen is a dialyzable substance, and that its concentration is reduced (and therefore the patient's body temperature rises) during hemodialysis.

Plasma iron, copper, and zinc in lizard Dipsosaurus dorsalis: effects of bacteria injection.

The effects of inoculation of desert iguanas (Dipsosaurus dorsalis) with heat-killed Aeromonas hydrophila on the plasma concentrations of iron, copper, and zinc, and the total iron-binding capacity have been determined. Plasma iron concentration and total iron-binding capacity fell significantly in inoculated lizards maintained at temperatures corresponding to those selected during fever. Plasma copper concentration did not change in response to inoculation (as determined at 24 h postinjection). Plasma zinc concentration fell in inoculated lizards regardless of whether the lizards were maintained at temperatures corresponding to those selected by afebrile or febrile lizards. There were no effects of varying the zinc concentration (corresponding to those observed in noninfected lizards, infected lizards, or at subnormal levels) on the in vitro growth rate of A. hydrophila. We hypothesize that the reduction in plasma zinc observed in infected mammals, and now in infected lizards, may have an effect (perhaps by some indirect pathway) on the in vivo growth rate of A. hydrophila.

Fever and reduced iron: their interaction as a host defense response to bacterial infection.

When rabbits are infected with Pasteurella multocida, the concentration of iron in their plasma decreases and their rectal temperature rises. To determine whether the rise in body temperature (fever) and the fall in plasma iron may be a coordinated host defense response, Pasteurella multocida were grown in vitro at various temperatures and iron concentrations. At afebrile temperatures the bacteria grew equally well at low or high concentrations of iron. However, when the temperature of the bath was raised to a febrile temperature the growth of the bacteria was inhibited by the low, but not the high, iron concentrations. These data support the hypothesis that one of the mechanisms behind the adaptive (or beneficial) role of fever is the reduced ability of pathogenic bacteria to grow well at elevated temperatures in an iron-poor medium.