title: Failure of interferon-gamma and tumor necrosis factor in mediating anemia of chronic disease in a mouse model of protracted septic peritonitis.
abstract: Interferon-gamma (IFN-gamma) is considered one of the main inflammatory cytokines contributing to the generation of anemia of chronic disease (ACD). In this study, we used a previously described murine model for ACD based on sublethal cecal ligation and puncture (CLP) with ensuing protracted peritonitis. Within 2 weeks after CLP, a moderate normochromic anemia with low serum iron concentration and preserved iron stores develops, which is consistent with ACD. In order to determine whether IFN-gamma contributes to the development of ACD in vivo, we neutralized IFN-gamma after CLP shortly before and during the phase of most severe bone marrow depression in order to prevent anemia. Additionally, we studied IFN-gamma receptor-deficient mice that underwent CLP. Two weeks after CLP, we determined the red blood cell count, hemoglobin concentration, hematocrit, serum iron concentration, and iron stores in spleens of wild-type mice, IFN-gamma receptor-deficient mice, and mice after neutralization of IFN-gamma. Neutralization of IFN-gamma after CLP could not prevent mice from becoming anemic. Accordingly, IFN-gamma receptor-deficient mice developed anemia to the same extent as wild-type mice. Serum iron concentration was lowered both in IFN-gamma receptor-deficient and wild-type mice. Iron stores in untreated IFN-gamma receptor-deficient mice were elevated compared to untreated wild-type mice. After CLP both IFN-gamma receptor-deficient and wild-type mice had equally overloaded iron stores. Additional neutralization of TNF in IFN-gamma receptor-deficient mice also did not attenuate CLP-induced anemia. Our results clearly demonstrate that neither IFN-gamma alone nor in combination with TNF is a mediator of ACD in our model with transient anemia induced by protracted septic peritonitis.
authors.affiliation: Department of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. thomas.schubert@klinik.uni-regensburg.de
authors.forename: Thomas E O
authors.initials: TE
authors.lastname: Schubert
authors.forename: Bernd
authors.initials: B
authors.lastname: Echtenacher
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
authors.forename: Daniela N
authors.initials: DN
authors.lastname: Männel
mesh_terms: D000740:Anemia / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004906:Erythrocyte Count; D005260:Female; D005838:Genotype; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007501:Iron / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010538:Peritonitis / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D018805:Sepsis / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D000906:Antibodies; D007371:Interferon-gamma; D007501:Iron; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor