TNF-independent development of transient anemia of chronic disease in a mouse model of protracted septic peritonitis.
TNF is considered one of the inflammatory cytokines and contributes mainly to the generation of anemia of chronic disease (ACD). In nude mice TNF has been reported to impair iron metabolism and erythropoiesis, leading to anemia with a low serum iron and preserved iron stores. In this work, we established a murine model for ACD based on sublethal cecal ligation and puncture (CLP) with ensuing protracted peritonitis. Starting on Day 3 after CLP, a severe protracted depression of erythropoiesis in the bone marrow was noted. Two weeks after CLP, we observed a moderate normochromic anemia, low serum iron concentration, and preserved iron stores consistent with transient ACD. To determine whether TNF contributes to the development of ACD in vivo, we neutralized TNF after CLP shortly before and during the phase of most severe bone marrow depression to prevent anemia. Additionally, we studied TNF-deficient mice undergoing CLP. Two weeks after CLP, we determined red blood count, hemoglobin concentration, hematocrit, serum iron concentration, and iron stores in spleens of wild-type mice, TNF-deficient mice, and mice after neutralization of TNF. Neutralization of TNF after CLP could not prevent mice from contracting anemia. Accordingly, TNF-deficient mice developed anemia to the same extent as wild-type mice. Serum iron concentration was lowered and iron stores were overloaded in both TNF-deficient and wild-type mice after CLP. Our results clearly demonstrate that TNF is not a mediator of ACD in our model with transient anemia induced by protracted septic peritonitis.
Schubert
Thomas
T
Department of Pathology, University of Regensburg, Regensburg, Germany. thomas.schubert@klinil.uni-regensburg.de
Echtenacher
Bernd
B
Hofstädter
Ferdinand
F
Männel
Daniela N
DN
D000740:Anemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001853:Bone Marrow / Q000503:physiopathology; D002432:Cecum; D004195:Disease Models, Animal; D004906:Erythrocyte Count; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000097:blood; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D007501:Iron / Q000097:blood; D008026:Ligation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010538:Peritonitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018805:Sepsis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*
D019138:Antibodies, Blocking; D006454:Hemoglobins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007501:Iron