scholarly journals Iron-controlled infection with Neisseria meningitidis in mice

1980 ◽  
Vol 29 (3) ◽  
pp. 886-891 ◽  
Author(s):  
B E Holbein
Keyword(s):  
Neisseria Meningitidis ◽  
Serum Iron ◽  
Reticuloendothelial System ◽  
High Serum ◽  
Iron Dextran ◽  
Working Hypothesis ◽  
Intraperitoneal Infection ◽  
Parenteral Iron

An iron-controlled infection was obtained after the intraperitoneal infection of Neisseria meningitidis strain M1011 into normal mice. The infection progressed rapidly but then disappeared in concert with the disappearance of plasma transferrin iron. Parenteral iron dextran enhanced and prolonged the infection in mice at dosages above 15 mg of Fe per kg. Studies on the distribution of iron dextran within the physiological iron pools and the importance of timing with the iron dextran addition indicated that high serum iron, available early during infection, was necessary to promote infection. High levels of iron in the reticuloendothelial system did not stimulate infection. A working hypothesis to explain the roles of iron in infection was developed: N. meningitidis obtains iron for growth from the transferrin pool, and iron dextran maintains transferrin iron levels during infection.

scholarly journals The hypoferremic response to acute inflammation is maintained in thalassemia mice even under parenteral iron loading

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11367
Author(s):  
Chanita Sanyear ◽  
Buraporn Chiawtada ◽  
Punnee Butthep ◽  
Saovaros Svasti ◽  
Suthat Fucharoen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Serum Iron ◽  
Acute Inflammation ◽  
Iron Homeostasis ◽  
Mrna Levels ◽  
Iron Dextran ◽  
Iron Loading ◽  
Wild Type ◽  
Altered Expression ◽  
Parenteral Iron

Background Hepcidin controls iron homeostasis by inducing the degradation of the iron efflux protein, ferroportin (FPN1), and subsequently reducing serum iron levels. Hepcidin expression is influenced by multiple factors, including iron stores, ineffective erythropoiesis, and inflammation. However, the interactions between these factors under thalassemic condition remain unclear. This study aimed to determine the hypoferremic and transcriptional responses of iron homeostasis to acute inflammatory induction by lipopolysaccharide (LPS) in thalassemic (Hbbth3/+) mice with/without parenteral iron loading with iron dextran. Methods Wild type and Hbbth3/+ mice were intramuscularly injected with 5 mg of iron dextran once daily for two consecutive days. After a 2-week equilibration, acute inflammation was induced by an intraperitoneal injection of a single dose of 1 µg/g body weight of LPS. Control groups for both iron loading and acute inflammation received equal volume(s) of saline solution. Blood and tissue samples were collected at 6 hours after LPS (or saline) injection. Iron parameters and mRNA expression of hepcidin as well as genes involved in iron transport and metabolism in wild type and Hbbth3/+ mice were analyzed and compared by Kruskal–Wallis test with pairwise Mann–Whitney U test. Results We found the inductive effects of LPS on liver IL-6 mRNA expression to be more pronounced under parenteral iron loading. Upon LPS administration, splenic erythroferrone (ERFE) mRNA levels were reduced only in iron-treated mice, whereas, liver bone morphogenetic protein 6 (BMP6) mRNA levels were decreased under both control and parenteral iron loading conditions. Despite the altered expression of the aforementioned hepcidin regulators, the stimulatory effect of LPS on hepcidin mRNA expression was blunt in iron-treated Hbbth3/+ mice. Contrary to the blunted hepcidin response, LPS treatment suppressed FPN1 mRNA expression in the liver, spleen, and duodenum, as well as reduced serum iron levels of Hbbth3/+ mice with parenteral iron loading. Conclusion Our study suggests that a hypoferremic response to LPS-induced acute inflammation is maintained in thalassemic mice with parenteral iron loading in a hepcidin-independent manner.

Parenteral Iron Therapy: A Single Institution's Experience Over a 5-Year Period

2005 ◽  
Vol 3 (6) ◽  
pp. 791-795 ◽  
Author(s):  
Christopher A. Laman ◽  
Scott B. Silverstein ◽  
George M. Rodgers
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Iron Sucrose ◽  
Iron Therapy ◽  
Iron Dextran ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Parenteral Iron ◽  
Parenteral Iron Therapy ◽  
Event Rates

Many patients require parenteral iron therapy for optimal correction of anemia, including cancer patients who require erythropoietic drugs. Available parenteral iron therapy options include iron dextran, iron gluconate, and iron sucrose. The purpose of this study is to summarize our institution's experience with parenteral iron therapy over a 5-year period, with a focus on comparative safety profiles. All patients receiving parenteral iron therapy over this period were included in the analysis. Chi-squared test and Fisher's exact test were used to compare the adverse event rates of each product. A total of 121 patients received 444 infusions of parenteral iron over this period. Iron dextran was the most commonly used product (85 patients) and iron sucrose was the least used (2 patients). Iron gluconate was used by 34 patients. Overall adverse event rates per patient with iron dextran and iron gluconate were 16.5% and 5.8%, respectively (P = .024). Premedication with diphenhydramine and acetaminophen before infusions of iron dextran reduced adverse event rates per infusion from 12.3% to 4.4% (P = .054). Test doses of iron dextran were used 88% of the time for initial infusions of iron dextran. All adverse events for all parenteral iron products were mild or moderate. There were no serious adverse events and no anaphylaxis was observed. Our results suggest that, if test doses and premedications are used, iron dextran is an acceptable product to treat iron deficiency.

Differential response of serum iron indices (SII) to iron dextran (ID) in hemodialysis patients.

1996 ◽  
Vol 59 (2) ◽  
pp. 155-155
Author(s):  
Alicia C.M. Alexander ◽  
Gary R. Matzke ◽  
Reginald F. Frye ◽  
Frank Bruns ◽  
Raymond Rault
Keyword(s):  
Serum Iron ◽  
Hemodialysis Patients ◽  
Differential Response ◽  
Iron Dextran

Hepcidin inhibition improves iron homeostasis in ferrous sulfate and LPS treatment model in mice

Drug Research ◽  
2021 ◽  
Author(s):  
Vishal Patel ◽  
Amit Joharapurkar ◽  
Samadhan Kshirsagar ◽  
Maulik Patel ◽  
Hiren Patel ◽  
...  
Keyword(s):  
Ferrous Sulfate ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
The Body ◽  
Rapid Screening ◽  
Iron Dextran ◽  
Liver Iron ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Lps Treatment

Abstract Background Hepcidin, a liver-derived peptide, regulates the absorption, distribution, and circulation of iron in the body. Inflammation or iron overload stimulates hepcidin release, which causes the accumulation of iron in tissues. The inadequate levels of iron in circulation impair erythropoiesis. Inhibition of hepcidin may increase iron in circulation and improve efficient erythropoiesis. Activin-like kinase (ALK) inhibitors decrease hepcidin. Methods In this work, we have investigated an ALK inhibitor LDN193189 for its efficacy in iron homeostasis. The effect of LDN193189 treatment was assessed in C57BL6/J mice, in which hepcidin was induced by either ferrous sulfate or lipopolysaccharide (LPS) injection. Results After two hours of treatment, ferrous sulfate increased serum and liver iron, serum hepcidin, and liver hepcidin expression. On the other hand, LPS reduced serum iron in a dose-related manner after six hours of treatment. LDN193189 treatment increased serum iron, decreased spleen and liver iron, decreased serum hepcidin and liver hepcidin expression in ferrous sulfate-treated mice, and increased serum iron in LPS-induced hypoferremia. We observed that ferrous sulfate caused a significantly higher increase in liver iron, serum hepcidin, and liver hepcidin than turpentine oil or LPS in mice. Iron dextran (intraperitoneal or intravenous) increased serum iron, but LDN193189 did not show hyperferremia with iron dextran stimulus. Conclusion Ferrous sulfate-induced hyperferremia can be a valuable and rapid screening model for assessing the efficacy of hepcidin inhibitors.

Characteristics of Iron Dextran Utilization in Man

Blood ◽  
1969 ◽  
Vol 34 (3) ◽  
pp. 357-375 ◽  
Author(s):  
PERRY A. HENDERSON ◽  
ROBERT S. HILLMAN
Keyword(s):  
Reticuloendothelial System ◽  
Prolonged Storage ◽  
Iron Level ◽  
Iron Dextran ◽  
Serum Iron Level ◽  
Iron Supply ◽  
Iron Deficient ◽  
Marrow Stroma ◽  
Ionic Iron ◽  
Iron Delivery

Abstract The major portion of iron dextran iron becomes available to the erythroid marrow only after uptake and release of ionic iron by the reticuloendothelial system. With large intravenous infusions, (1000-2000 mg.), the rate of removal of the iron dextran complex from plasma is enough to supply the marrow with more than 200 mg. of iron/day. However, in the present studies the observed rate of iron delivery to the erythroid marrow was far below this level. Although iron supply immediately after infusion was sufficient to permit marrow production to rise to 4-6 times normal, this was maintained for less than two weeks. With time, reticuloendothelial iron dextran stores became less available, the serum iron level fell and marrow production was restricted to levels below twice normal. In fact, large infusion doses and prolonged storage may have made a portion of the iron dextran stores completely unavailable. Thus, an iron deficient type of erythropoiesis appeared in some patients while iron dextran stores were still readily visible on examination of marrow stroma.

scholarly journals IRON METABOLISM

Blood ◽  
1950 ◽  
Vol 5 (11) ◽  
pp. 983-1008 ◽  
Author(s):  
CLEMENT A. FINCH ◽  
MARK HEGSTED ◽  
THOMAS D. KINNEY ◽  
E. D. THOMAS ◽  
CHARLES E. RATH ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Serum Iron ◽  
Iron Absorption ◽  
Binding Protein ◽  
The Body ◽  
Iron Binding ◽  
Body Iron ◽  
Iron Administration ◽  
Parenteral Iron ◽  
Iron Binding Protein

Abstract On the basis of experimental and clinical observations and a review of the literature, a concept of the behavior of storage iron in relation to body iron metabolism has been formulated. Storage iron is defined as tissue iron which is available for hemoglobin synthesis when the need arises. This iron is stored intracellularly in protein complex as ferritin and hemosiderin. It would appear that wherever the cell is functionally intact, such iron is available for general body needs. Iron is transported by a globulin of the serum to and from the various tissues of the body to satisfy their metabolism. Surplus iron carried by this iron-binding protein is deposited chiefly in the liver. Storage iron may be increased in two ways. The first mechanism results from the inability of the body to excrete significant amounts of iron. Because of this, any decrease in circulating red cell iron (any anemia other than blood loss or iron deficiency anemia) is accompanied by a shift of iron to the tissue compartment. The total amount of body iron remains constant and is merely redistributed. This is to be contrasted with the absolute increase in body iron and enlarged iron stores which follow excessive iron absorption or parenteral iron administration. Enlarged iron stores in either instance may be evaluated by examination of sternal marrow or determination of the serum iron and saturation of the iron binding protein In states of iron excess, differences in initial distribution are observed, depending on the route of administration and type of iron compound employed. Iron absorbed from the gastro-intestinal tract and soluble iron salts injected in small amounts are transported by the iron-binding protein of the serum and stored predominantly in the liver. Colloidal iron given intravenously is taken up by the reticulo-endothelial tissue. Erythrocytes appear to localize in greatest concentration in the spleen, while greater amounts of hemoglobin iron are found in the renal parenchyma. These latter differences in distribution reflect the capacity of various body tissues to assimilate different iron compounds, which while present in the plasma are not carried by the iron-binding protein. Over a period of time an internal redistribution of iron from these various sites occurs through the serum iron compartment. The liver becomes progressively loaded with iron. When the capacity of the liver to store iron is exceeded, the serum iron increases and secondary tissue receptors begin to fill with iron. That iron in large amounts is toxic to tissues is suggested by the occurrence of fibrosis in the organs most heavily laden with iron. This sequence of events, whether following excessive iron absorption or parenteral iron administration is believed to be responsible for the clinical and pathologic picture of hemochromatosis.

Differences in virulence for mice between disease and carrier strains of Neisseria meningitidis

1981 ◽  
Vol 27 (7) ◽  
pp. 738-741 ◽  
Author(s):  
Bruce E. Holbein
Keyword(s):  
Neisseria Meningitidis ◽  
Model System ◽  
Iron Dextran ◽  
Good Assessment ◽  
High Virulence

The virulences of 11 prototype strains of Neisseria meningitidis, which had been used in the development of the serotyping scheme for serogroup B meningococci, were examined in mice treated with iron dextran. These strains, together with those previously examined, allowed for a good assessment of the virulence differences between carrier and disease strains. All of a total of 17 disease strains displayed virulence for mice (60% with high virulence), whereas only approximately 50% of 13 carrier strains possessed virulence (only 15% with high virulence).Because the ability to initiate infection in mice is independent of exogenous iron, this model system for infection appears particularly suited to studies of the physiological bases for virulence in N. meningitidis.

RNAi-Mediated Inhibition of Tmprss6 Elevates Hamp1 Expression and Reduces Serum Iron Levels in Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1045-1045 ◽  
Author(s):  
Ivanka Toudjarska ◽  
Zuhua Cai ◽  
Tim Racie ◽  
Stuart Milstein ◽  
Brian R Bettencourt ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Iron ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Elevated Serum ◽  
High Serum ◽  
Therapeutic Modality ◽  
Deficiency Anemia ◽  
Loss Of Function ◽  
Hepcidin Expression

Abstract Abstract 1045 The liver hormone Hepcidin (encoded by Hamp1) regulates serum iron levels by controlling the efflux of iron from intestinal enterocytes and macrophages. Maintaining sufficient iron levels to support erythropoiesis while preventing iron overload requires tight control of Hepcidin expression. Transcription of Hamp1 in hepatocytes is stimulated by high serum iron levels, via Transferrin Receptor signaling, as well as by activation of the BMP/SMAD pathway. The membrane serine protease Matriptase-2 (encoded by Tmprss6) inhibits BMP induced Hamp1 induction through the regulation of the BMP co-receptor, Hemojuvelin. In humans, loss of function mutations in TMPRSS6 lead to elevated Hepcidin levels resulting in iron-resistant iron-deficiency anemia (IRIDA). In diseases associated with iron overload, such as Thalassemia intermedia (TI) and Familial Hemochromatosis (FH), Hepcidin levels are low despite elevated serum iron concentrations. Studies in murine models of TI and FH have shown that elevating Hepcidin levels by genetic inactivation of Tmprss6 can prevent iron overload and correct aspects of the disease phenotype. Therefore, therapeutic strategies aimed at specifically inhibiting Tmprss6 expression could prove efficacious in these, and other, iron overloading diseases. Here we show that systemic administration of a potent lipid nanoparticle (LNP) formulated siRNA directed against Tmprss6 leads to durable inhibition of Tmprss6 mRNA in the mouse liver, with concomitant elevation of Hamp1 expression. This leads to significant decreases in serum iron concentration and Transferrin saturation, along with changes in hematologic parameters consistent with iron restriction. Further testing in mouse genetic models of TI and FH will support the rationale for developing LNP formulated Tmprss6 siRNA as a novel therapeutic modality. Disclosures: Toudjarska: Alnylam Pharmaceuticals, Inc.: Employment. Cai:Alnylam Pharmaceuticals, Inc.: Employment. Racie:Alnylam Pharmaceuticals, Inc.: Employment. Milstein:Alnylam Pharmaceuticals, Inc.: Employment. Bettencourt:Alnylam Pharmaceuticals, Inc.: Employment. Hettinger:Alnylam Pharmaceuticals, Inc.: Employment. Sah:Alnylam Pharmaceuticals, Inc.: Employment. Vaishnaw:Alnylam Pharmaceuticals, Inc.: Employment. Bumcrot:Alnylam Pharmaceuticals, Inc.: Employment.

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