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The anemia of infection is associated with a number of alterations in iron metabolism. Previous studies (1-4) have shown that, with the development of inflammation, hypoferremia occurs and a decrease takes place in the concentration of the metal binding protein in the plasma. When iron is given by mouth, there is little change in the level of plasma iron and, following the intravenous injection of iron, only a transient rise in the plasma iron develops. These findings have suggested that diversion of iron from the plasma takes place in inflammation and infection. Studies in experimental animals have shown that iron is diverted primarily to the liver and spleen. Whether this iron is simply stored, since less can be used in the face of diminished hemoglobin production, or performs a special function in connection with the presence of inflammation, is unknown. These findings contrast with those associated

Neutrophil kinetics of acute experimental infection were studied with diisopropylfluorophosphate-32P labeling in 31 dogs inoculated intra- bronchially with pneumococci. In vitro neutrophil labeling indicated a rapid transit time through the blood in early infections, with an elevated marginal granulocyte pool sometimes preceding an elevation of the circulating granulo- cyte pool. 13 hr after infection, the circulating and total blood granulocyte pools were increased but the rate of neutrophil transit through the blood was normal. During the recovery from infection there was a marked prolongation of neutrophil blood transit time, suggesting virtually complete cessation of bone marrow release of neutrophils into the blood. Labeling of neutrophils in vivo indicated an increased rate of emptying of the bone marrow storage pool proportional to the severity of infection as measured by the fever index. The change in the blood ratio of nonsegmented to segmented neutrophils was a much more accurate index of the severity of infection than the blood granu- locyte concentration, correlating significantly with the fever index.

Reticulated-siderocytes (reticulocytes which contain siderotic granules), obtained from the circulation of pigs after vigorous phlebotomy, were incubated in vitro. A rapid disappearance of granules from the reticulocytes was observed over 24 hr. Simultaneously with the decrease in granules, soluble ferritin accumulated in the media and siderotic granules developed in monocytes. The disappearance of the granules from the reticulated-siderocytes was oxygen-dependent and the loss of granules and the accumulation of ferritin in the media were both prevented by the addition of cyanide or dinitrophenol. It is concluded that the ferritin aggregates in the granules of reticulated-siderocytes are dispersed intracellularly into soluble ferritin, that soluble ferritin is excreted from the cell, and that one or both of these steps is dependent upon oxidative metabolism. Blood monocytes are capable of taking up soluble ferritin from the media and converting this into siderotic granules. Thus, a reticulocyte to plasma to monocyte ferritin pathway has been described.

Changes in the free erythrocyte protoporphyrin, plasma iron, serum iron-binding capacity and plasma copper in normal individuals and in various diseases associated with anemia have been investigated previously in this laboratory (1). The present observations were carried out to determine the "chemical pattern" of the blood in the pregnant state.

The mechanism by which adrenocortical steroids induce granulocytosis in man has been investigated using granulocytes labeled with radioactive diisopropylfluorophosphate. After an intravenous injection of 200 mg of cortisol was given to five normal subjects, the mean value for the total blood granulocyte pool increased from 79 to 138 x 10(7) cells per kg of body weight and reflected an increase in the size of both the circulating granulocyte pool and the marginal granulocyte pool. When granulocytes in the circulation were labeled with diisopropylfluorophosphate and granulocytosis was induced later by the intravenous administration of cortisol, the rate of decline of granulocyte specific activity was increased, indicating that the blood pool was being diluted at an accelerated rate by unlabeled cells entering from the bone marrow. The rate of egress of granulocytes from the blood pool to an inflammatory exudate was studied by the "skin window" technique. After the administration of cortisol, there was a mean reduction in the cellularity of induced inflammatory exudates of 75%. However, this reduction in cellularity varied considerably from subject to subject (45-98%). From these studies we can infer that steroids induce an absolute granulocytosis by decreasing the rate of egress of cells from the total blood granulocyte pool as well as by increasing the influx of cells from the bone marrow. By model simulation studies of the non-steady state induced by cortisol injection, it has been possible to quantitate these rate changes. In the present studies cortisol injection resulted in a mean decrease in blood granulocyte egress of 74% (1-99%) and a mean increase in cell inflow of 450% (300-750%).

Superoxide dismutase exerted a pronounced inhibitory effect upon xanthine oxidase-mediated reduction of iron in ferritin, ferric chloride, or ferric ADP. Maximal inhibition was observed when the superoxide dismutase concentration was only about 1% of that found in normal porcine liver. These observations indicate that superoxide anion radical is an intermediate in the reduction of iron by xanthine oxidase in vitro but not in vivo.