title: Infection-stimulated anemia results primarily from interferon gamma-dependent, signal transducer and activator of transcription 1-independent red cell loss.
abstract: BACKGROUND
  Although the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines, the mechanisms by which cytokines induce anemia are poorly defined. This study focused on the mechanism research.
  
  
  METHODS
  Different types of mice were infected perorally with Toxoplasma gondii strain ME49. At the indicated times, samples from each mouse were harvested, processed, and analyzed individually. Blood samples were analyzed using a Coulter Counter and red blood cell (RBC) survival was measured by biotinylation. Levels of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and inducible protein 10 (IP-10) mRNA in liver tissue were measured by real-time polymerase chain reaction.
  
  
  RESULTS
  T. gondii-infected mice exhibited anemia due to a decrease in both erythropoiesis and survival time of RBC in the circulation (P < 0.02). In addition, infection-stimulated anemia was associated with fecal occult, supporting previous literature that hemorrhage is a consequence of T. gondii infection in mice. Infection-induced anemia was abolished in interferon gamma (IFNγ) and IFNγ receptor deficient mice (P < 0.05) but was still evident in mice lacking TNF-α, iNOS, phagocyte NADPH oxidase or IP-10 (P < 0.02). Neither signal transducer and activator of transcription 1 (STAT1) deficient mice nor 129S6 controls exhibited decreased erythropoiesis, but rather suffered from an anemia resulting solely from increased loss of circulating RBC.
  
  
  CONCLUSIONS
  Infection-stimulated decrease in erythropoiesis and losses of RBC have distinct mechanistic bases. These results show that during T. gondii infection, IFNγ is responsible for an anemia that results from both a decrease in erythropoiesis and a STAT1 independent loss of circulating RBC.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Yuhuangding Hospital, Yantai, Shandong 264000, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000740:Anemia / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004912:Erythrocytes / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor
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