Pro-Inflammatory Cytokine-Mediated Anemia: Regarding Molecular Mechanisms of Erythropoiesis

Morceau, Franck; Dicato, Mario; Diederich, Marc

doi:10.1155/2009/405016

Cited by 128 publications

(95 citation statements)

References 135 publications

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“…8). A correlation of high TNF-␣ with higher bacterial loads and more severe anemia is consistent with published studies linking TNF-␣ to impaired erythropoiesis and erythrocyte membrane injury (23,49). Increased duodenal expression of Fpn1 supports a systemic need for iron and increased dietary absorption in response to reactive erythropoiesis.…”

Section: Discussionsupporting

confidence: 86%

Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice

et al. 2015

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e The Gram-negative intracellular bacterium Salmonella enterica serovar Typhimurium causes persistent systemic inflammatory disease in immunocompetent mice. Following oral inoculation with S. Typhimurium, mice develop a hematopathological syndrome akin to typhoid fever with splenomegaly, microcytic anemia, extramedullary erythropoiesis, and increased hemophagocytic macrophages in the bone marrow, liver, and spleen. Additionally, there is marked loss of iron from the spleen, an unanticipated result, given the iron sequestration reported in anemia of inflammatory disease. To establish why tissue iron does not accumulate, we evaluated multiple measures of pathology for 4 weeks following oral infection in mice. We demonstrate a quantitative decrease in splenic iron following infection despite increased numbers of splenic phagocytes. Infected mice have increased duodenal expression of the iron exporter ferroportin-1, consistent with increased uptake of dietary iron. Liver and splenic macrophages also express high levels of ferroportin-1. These observations indicate that splenic and hepatic macrophages export iron during S. Typhimurium infection, in contrast to macrophage iron sequestration observed in anemia of inflammatory disease. Tissue macrophage export of iron occurs concurrent with high serum concentrations of interferon gamma (IFN-␥) and interleukin 12 (IL-12). In individual mice, high concentrations of both proinflammatory (tumor necrosis factor alpha [TNF-␣])and anti-inflammatory (IL-10) cytokines in serum correlate with increased tissue bacterial loads throughout 4 weeks of infection. These in vivo observations are consistent with previous cell culture studies and suggest that the relocation of iron from tissue macrophages during infection may contribute to anemia and also to host survival of acute S. Typhimurium infection.T yphoid fever is acquired upon oral ingestion of food or water contaminated with Salmonella enterica serovar Typhi or Paratyphi and remains a serious threat to public health, especially in developing countries (1). Human typhoid fever causes a broad range of clinical signs, including splenomegaly, neuropathy, and hematopathology, such as cytopenias (2), that have been modeled in laboratory mice infected with Salmonella enterica serovar Typhimurium (3). Inbred mouse strains with differing genetic backgrounds are characterized as either sensitive or resistant to S. Typhimurium. Sensitivity to the intracellular bacterial infection is caused by genetic deficiencies in the innate or adaptive immune system (4, 5). For instance, mice lacking the cation transporter Nramp1 (Slc11a1), a regulator of cellular iron metabolism, are extremely sensitive to infection. Nramp1 ϩ mice are considered resistant to S. Typhimurium, because infection is generally nonfatal (6-8). Resistant mice infected by natural oral inoculation develop systemic infection with an acute hematopathological syndrome similar to that of humans with typhoid fever, including fever, anemia, inflammatory disease characterized by periph...

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Section: Discussionsupporting

confidence: 86%

Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice

et al. 2015

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“…Concentration of red blood cell and hemoglobin in the peripartal period decrease [3,23], also as a result of inflammation [24] while these concentration increases in cows treated with NSAID [29] what matches with our findings.…”

Section: Discussionsupporting

confidence: 90%

Hematological Parameters in Cows in Early Lactation Treated with Ketoprofen and their Relationship with Lipid Mobilization and Ketogenesis

Kovačević

Stojanović

Cincović

et al. 2016

Acta Scientiae. Vet.

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Background: Dairy cows are exposed to numerous hematological and biochemical changes, what is bringing cows into the state of increased metabolic activity and physiological adaptations. These adaptive processes have resulted in increased lipid mobilization and ketogenesis with increased concentration of non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB). As a non steroidal anti-inflammatory drug, ketoprofen produces anti-inflammatory effects. The main objective of the present study was to found relationship between hematological parameters and ketoprofen administration and high lipid mobilization and ketogenesis in cows treated with ketoprofen immediately after calving. Materials, Methods & Results: Ketoprofen was used (3 mg/kg body weight) intramuscularly for three consecutive days post-partum on 15 cows of Holstein-Friesian breed. Cows of the control group (n = 15) were not treated with ketoprofen. Blood samples were collected at the day of calving, in the first and in the second week after parturition from the coccygeal vein of the both groups. Hematological parameters (erythrocytes, hemoglobin, neutrophils, lymphocytes and mean platelet volume) were determined on the automatic hematological counter. Metabolic parameters (NEFA, BHB) were determined by standard colorimetric kits using a semi-automatic biochemistry analyzer. Student's t-test was used to determine the influence of the application of ketoprofen to the hematological parameters. The data analysis was performed using SPSS, version 19.0, software package for Microsoft Windows (IBM, Armonk, NY, USA). The results of comparison with (P < 0.05) were considered to represent statistically significant differences. Difference in correlation test between NEFA and BHB and other blood parameters in experimental and control group of cows were determined by the Fischer r-to-z transformation. The research results show that there was a increased red blood cell count and a higher concentration of hemoglobin (P < 0.05), fewer neutrophils (P < 0.01), lower number of lymphocytes (P < 0.01) and fewer mean platelet volume in cows that received ketoprofen after calving than those of the control. Determined hematological parameters and values of NEFA and BHB are in correlation. The correlation coefficients were significantly lower in the experimental group of cows. The intensity of the connection between hematological parameters and value of NEFA and BHB decreases. Discussion: It is well known that dairy cows with excessive adiposity manifest a low-grade inflammation and that elevated NEFA concentrations present positive risk factors for many proinflammatory diseases. Analyzing the results in this examination, it has been noticed that the increase of NEFA and BHB after calving were significantly lower in group of cows treated with ketoprofen. Also, determined hematological parameters and values of NEFA and BHB are in correlation. The intensity of these connection decreases in ketoprofen treated cows. In current study, in cows treated with ketoprofen t...

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“…4,5 Additionally, several cytokines, including tumor necrosis factor-a (TNF-a), interferon-g, and interleukin 1 (IL-1), negatively regulate the production and bioactivity of erythropoietin, 6,7 as well as the proliferation, survival, and differentiation of erythroid progenitors cells. 8,9 The hepatic hormone hepcidin (Hamp), 10 the master regulator of iron metabolism, is also a known mediator of AI. 3,11 By binding the iron-exporter ferroportin, 12 Hamp causes its internalization and degradation in lysosomes, 13 thus limiting iron recycling and availability for hemoglobin (Hb) synthesis.…”

Section: Introductionmentioning

confidence: 99%

Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus

Gardenghi

Renaud

Meloni

et al. 2014

Blood

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Key Points• Investigation of the distinct roles of hepcidin and interleukin 6 on iron metabolism and inflammation in the onset and resolution of AI.Anemia of inflammation (AI) is commonly observed in chronic inflammatory states and may hinder patient recovery and survival. Induction of hepcidin, mediated by interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several translational studies have been directed at neutralizing hepcidin overexpression as a therapeutic strategy against AI. However, additional hepcidin-independent mechanisms contribute to AI, which are likely mediated by a direct effect of inflammatory cytokines on erythropoiesis. In this study, we used wild-type, hepcidin knockout (Hamp-KO) and interleukin 6 knockout (IL-6-KO) mice as models of AI. AI was induced with heat-killed Brucella abortus (BA). The distinct roles of iron metabolism and inflammation triggered by interleukin 6 and hepcidin were investigated. BA-treated wild-type mice showed increased expression of hepcidin and inflammatory cytokines, as well as transitory suppression of erythropoiesis and shortened red blood cell lifespan, all of which contributed to the severe anemia of these mice. In contrast, BA-treated Hamp-KO or IL-6-KO mice showed milder anemia and faster recovery compared with normal mice. Moreover, they exhibited different patterns in the development and resolution of anemia, supporting the notion that interleukin 6 and hepcidin play distinct roles in

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Pro-Inflammatory Cytokine-Mediated Anemia: Regarding Molecular Mechanisms of Erythropoiesis

Cited by 128 publications

References 135 publications

Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice

Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice

Hematological Parameters in Cows in Early Lactation Treated with Ketoprofen and their Relationship with Lipid Mobilization and Ketogenesis

Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus

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