Lymphocyte subpopulations in the thymus, lymph nodes and spleen of iron-deficient and rehabilitated mice.

Three groups of weanling female mice were fed one of two iron-deficient diets (5 and 12 mg Fe/kg diet) or a normal diet (30 mg Fe/kg diet) for 6 wk. A control pair-fed group was included. Seven mice received the 5 mg Fe/kg diet for 6 wk, then were rehabilitated using the 30 mg Fe/kg diet for 10 d. Mice fed the 5 mg Fe/kg diet were moderately iron-deficient, as shown by indices of iron status. No significant differences were observed in thymus weight or in the proportion and number of thymocyte subsets in thymuses of anemic, moderately iron-deficient and control mice. Thymus weight was decreased in pair-fed mice. No significant difference was found in lymph node subsets. In the spleen of anemic mice, the proportions and total number of Thy-1+ splenocytes, CD4-8+ and CD4+8- cells were very low compared with control (P less than 0.01) and iron-deficient (P less than 0.02) mice. The decrease was not only observed for the percentage of subsets but also for the absolute number of cell subtypes per spleen. Thy-1+ splenocyte subpopulations were normalized after rehabilitation. These quantitative modifications could explain alterations in the blastogenic response of splenic lymphocytes described by other authors.

Folate status and the immune system.

Folic acid plays a crucial role in DNA and protein synthesis, suggesting that every mechanism in which cell proliferation intervenes may be altered. Cell-mediated immunity is especially affected by folate deficiency: the blastogenic response of T lymphocytes to certain mitogens is decreased in folate-deficient humans and animals, and the thymus is preferentially altered. The effects of folic acid deficiency upon humoral immunity have been more thoroughly investigated in animals than in humans, and the antibody responses to several antigens have been shown to decrease. Conversely, the phagocytic and bactericidal capacities of polymorphonuclear cells have been studied mainly in folate-deficient humans. However results in this field are controversial. Alterations in immune system functions could lead to decreased resistance to infections, as commonly observed in folate-deficient humans and animals.

Effect of folic acid deficiency upon lymphocyte subsets from lymphoid organs in mice.

1. Three groups of weanling C57BL/6 female mice were fed one of two folate-deficient diets (0 and 0.1 mg folic acid/kg diet) or a normal folate-containing diet (2 mg folic acid/kg diet) for 8 weeks. A control pair-fed group was introduced with the most severe folate-deficient diet. Seven mice were fed the 0 mg folic acid/kg diet for 8 weeks, then rehabilitated (R) on the 2 mg folic acid/kg diet for 10 days. 2. Mice fed 0 mg folic acid/kg diet were severely folate-deficient (SFD), whereas mice fed 0.1 mg folic acid/kg diet were moderately folate-deficient (MFD), as shown by their folate status parameters. 3. Thymus weight, thymocyte content and positive immature CD4+8+ cells were decreased in SFD mice compared to controls. These values were normalized after 10 days of rehabilitation. 4. Mesenteric lymph node cells were apparently not affected by folate deficiency. 5. The proportion of Thy-1+ splenocytes was mildly lower in SFD mice than in controls. In R mice, mean spleen weight and spleen cellularity were increased compared to the other groups, but the proportions of Thy-1+, CD4+8- and CD4-8+ cells were markedly lower than control values.

Effects of iron deficiency upon the antibody response to influenza virus in rats.

The effects of severe and moderate iron deficiency upon the antibody response to influenza virus were investigated in rats. Three groups of weanling male Wistar rats were fed one of two iron-deficient diets (5 mg and 15 mg iron/kg diet) or a normal iron-containing diet (35 mg iron/kg diet). A group of individually pair-fed rats was introduced with the low iron-consuming rats. The effects of the diets upon various iron status parameters were followed during the 4th, 5th, 6th, and 7th week of diet. After 4 weeks of feeding different diets, an intraperitoneal injection of inactivated influenza virus A/New Jersey/76 was performed and a recall injection was done at 5 weeks. Primary and secondary antibody responses were assayed. Rats were sacrificed at 7 weeks of diet. After 4 weeks of feeding different diets, the rats fed the 5 mg iron/kg diet were severely anemic and rats fed 15 mg iron/kg diet were moderately iron-deficient, as shown by their iron status parameters. Growth was delayed in anemic and matched pair-fed rats. A primary antibody response was almost nonexistent in all groups. Secondary antibody titers were significantly weaker in anemic rats than in ad libitum controls, but were not different from those of pair-fed rats. This response was similar in moderately iron-deficient, ad libitum, and pair-fed rats. These results show that antibody synthesis in response to the influenza virus vaccine is preserved in moderate iron deficiency but is reduced in severe anemia. The reduction in energy consumption associated with severe iron deficiency in the rat could play a part in the altered humoral response.

Effect of decreased food consumption during iron deficiency upon growth rate and iron status indicators in the rat.

Weanling Wistar rats were given a low-iron diet (4-5 mg Fe/kg), a medium-iron diet (20 mg Fe/kg) or a control diet (40 mg Fe/kg) for 7 weeks. Pair-fed rats received the control diet in amounts equivalent to that consumed by animals on a low-Fe diet. Blood samples from the tail vein were taken after 4 weeks of diet and weekly during the following 3 weeks for determination of iron status parameters. Animals were weighed weekly. After 4 weeks of diet, the rats fed the 5 mg iron/kg diet were severely anemic and rats fed 20 mg iron/kg diet were moderately iron-deficient. Ad libitum and pair-fed controls had normal iron status. Total liver iron stores were lowest in anemic rats (p less than 0.001) and were also low in moderately iron-deficient animals (p less than 0.05). Growth rates decreased early in anemic and pair-fed rats. Both groups were smaller than controls and moderately iron-deficient rats after 2 weeks (p less than 0.05) and this continued until the end of the experiment (p less than 0.001). Body weights of pair-fed rats were lower than those of anemic rats from the 1st to the 3rd week of diet; thereafter, differences between the two groups were no longer significant.

Relationship between selenium, immunity and resistance against infection.

1. Food selenium content, selenium supply and selenium needs are presented, along with methods of evaluation of selenium status. Glutathione peroxidase, a selenium-containing enzyme, is ubiquitous in the organism. 2. Some experimental studies on animal models reported a positive relationship between selenium status and resistance against infections. 3. Only one study in humans concerned the mechanisms of immune functions in selenium deficiency. Several experimental works suggest that severe selenium deficiency compromises T-cell dependent immune functions such as the blastogenic response to mitogens, but selenium deficiency was concomitant with vitamin E deficiency in most of them. Delayed hypersensitivity response is controversial in selenium-supplemented rats and guinea-pigs. 4. Selenium deficiency in animals decreases the antibody response, especially if associated with vitamin E deficiency. Low dietary selenium supplementation of healthy animals has a positive effect upon humoral responses. 5. Despite some controversies, most experimental studies on selenium-deficient animals report normal phagocytosis and an altered bactericidal capacity of neutrophils. The decrease in glutathione peroxidase activity of polymorphonuclear cells following selenium deficiency could explain some of these alterations. 6. Splenic Natural Killer cells activity is enhanced in selenium-supplemented, healthy animals.

Iron status, immune capacity and resistance to infections.

1. The importance of iron on immune functions is reviewed. 2. The consequences of iron deficiency upon resistance to infection in men (adults and children) and animals are controversial. 3. Cellular immunity is often altered in iron-deficient humans and in murine species. 4. Humoral immune responses seem far less affected in iron-deficient humans than is cellular immunity, but is impaired in iron-deficient animals. Results on complement are scarce and controversial. 5. There is almost no perturbation of phagocytosis but bactericidal activity is decreased in most studies on iron-deficient subjects. 6. Natural Killer activity is decreased in iron-deficient mice. Iron deficiency also affects lymphokine production in mice and rats.

Effects of different degrees of iron deficiency on cytochrome P450 complex and pentose phosphate pathway dehydrogenases in the rat.

Four groups of weanling male rats were fed one of three iron-deficient diets (6, 18 and 23 mg iron/kg diet) or a normal iron-containing diet (41 mg iron/kg diet) for 30 d. The effects of the diets on various iron status parameters were determined and four enzymes were assayed: cytochrome P450 (P450) and NADPH cytochrome P450 reductase (P450-RED) in liver and intestine microsomes, and glucose-6-phosphate dehydrogenase (G6P-DH) and 6-phosphogluconate dehydrogenase (6PG-DH) in liver, intestine and erythrocyte cytosol. Rats fed 6 mg iron/kg diet were severely anemic, whereas rats fed 18 or 23 mg iron/kg diet were moderately or mildly iron-deficient, as shown by their hemoglobin levels, hematocrit, red blood cell parameters, erythrocyte protoporphyrin and liver iron stores. P450 concentration and P450-RED activity in liver were unaffected by iron deficiency, but P450 concentration was markedly lower in the intestine of the three iron-deficient groups than in the controls. Activities of G6P-DH and 6PG-DH were not impaired in liver or intestine, except that liver 6PG-DH activity of severely anemic rats was less than that of control rats. However, severe and moderate iron deprivation resulted in a stimulation of G6P-DH and 6PG-DH activities per million erythrocytes. These results demonstrate that even moderate iron deficiency may alter fundamental enzymatic systems intervening in drug metabolism and in the pentose phosphate pathway.

[Comparison of 2 methods for evaluating the prevalence of anemia in young children]. / Comparaison de deux méthodes d'évaluation de la prévalence de l'anémie chez le jeune enfant.

Prevalence of anemia was estimated by two methods in 1235 healthy children 10 months old undergoing a free-of-charge medical checkup in a Parisian Child Health Examination Center. According to the classical method, the frequency of anemia, defined as the percentage of children with hemoglobin concentration below the WHO cut-off point (11 g/dl), amounts to 16.8% of 797 French children, 24.0% of 289 North African children and 43.6% of 149 sub-saharan children. The second method defines the frequency of anemia as the percentage of children whose hemoglobin values are shifted downwards relative to a gaussian hemoglobin distribution in non-anemic children. According to this method, anemia was present in 0.8%, 5.4% and 12.6% of children, respectively. The conventional cut-off point probably tends to overestimate the true frequency of anemia in this age group.