Since hypoferremia is so consistently associated with the anemia of infection (1), and since injected iron appears to be diverted from the plasma in infection (1, 2), it seemed desirable to determine the fate of the diverted iron.In this study, radioactive iron was injected intravenously into normal rats and in rats with acute inflammation. The blood and tissues were then analyzed after a period of time for radioactivity. Preliminary studies were made in which only the blood and liver were analyzed in order to determine the appropriate amount of iron to employ. Radioactive iron was also injected intravenously into dogs, and analyses were carried out on a number of tissues, including the exudates.
METHODSThe radioactive iron used in these studies was injected as ferric chloride in physiological saline. For the rats, the concentration was adjusted so that about 0.2 ml. was injected for each 100 grams body weight. In all the rats the same tuberculin syringe was employed for this purpose. In order to be certain that the solution did not enter subcutaneously, the vein on the lateral aspect of the tail was exposed under nembutal anesthesia and the solution was injected intravenously. In one experiment Fe was injected intraperitoneally.Inflammation was produced by the intramuscular injection of 0.5 ml. of turpentine. Robscheit-Robbins and Wlhipple (3) have shown that the resulting sterile abscess can be compared with a bacterial abscess. In some animals, 0.5 ml. of a mixed culture of S. aureus and E. coli was injected intramuscularly. Injections of bacteria or turpentine were made about 2 hours before Fe was administered.The methods for preparing and electroplating the Fe from the biological samples have been described elsewhere (4). Blood volume was estimated by assuming that the normal mammal possesses 80 ml. blood per kgm. body weight. Hemoglobin was determined in a representative sample of the tissue to be analyzed for radio-
The pronounced and persistent hypoferremia which accompanies infection, and the rapidity with which intravenously injected iron is removed when given in such cases (1), have led to the suggestion that the anemia of chronic infection results from a local iron deficiency in the bone marrow. Since the quantity of free protoporphyrin in the erythrocytes has been found increased in association with the anemia of infection, the possibility exists that this anemia is the consequence of deficient formation of hemoglobin resulting from a lack of iron. The studies to be described here were designed to test the validity of this hypothesis. Iron was infused continuously in patients with chronic infection in order to determine whether, by raising the iron level to the normal value, synthesis of hemoglobin could be induced. These observations have made it possible to study the rate and degree of diversion of iron from the plasma in infection. Several observations also have been made of the uptake of intravenously administered radioactive iron by the red cells of patients with acute and chronic infections. Evidence will be presented in this communication suggesting that while a rapid removal from the plasma of injected iron occurs in infection, another factor, rather than lack of iron, may be responsible for the development of anemia.
METHODSFerrous ascorbate was used for the continuous infusion studies. A 2 per cent aqueous solution was carried through a Seitz filter. With a syringe this was added to a bottle containing 500 ml. sterile 5 per cent glucose solution; thus, the final solution contained 4 mgm. of iron per 100 ml. Since-ferrous ascorbate is a complex with varying amounts of iron (2), each lot had to be analyzed, and the amount used varied accordingly. To obtain quickly the elevated plasma iron level, a single dose of
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