title: Hemophagocytosis causes a consumptive anemia of inflammation.
abstract: Cytopenias of uncertain etiology are commonly observed in patients during severe inflammation. Hemophagocytosis, the histological appearance of blood-eating macrophages, is seen in the disorder hemophagocytic lymphohistiocytosis and other inflammatory contexts. Although it is hypothesized that these phenomena are linked, the mechanisms facilitating acute inflammation-associated cytopenias are unknown. We report that interferon γ (IFN-γ) is a critical driver of the acute anemia observed during diverse microbial infections in mice. Furthermore, systemic exposure to physiologically relevant levels of IFN-γ is sufficient to cause acute cytopenias and hemophagocytosis. Demonstrating the significance of hemophagocytosis, we found that IFN-γ acts directly on macrophages in vivo to alter endocytosis and provoke blood cell uptake, leading to severe anemia. These findings define a unique pathological process of broad clinical and immunological significance, which we term the consumptive anemia of inflammation.
authors.affiliation: Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Zoller
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Lykens
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Terrell
authors.forename: Julio
authors.initials: J
authors.lastname: Aliberti
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
mesh_terms: D000740:Anemia / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002469:Cell Separation; D006224:Cricetinae; D004705:Endocytosis; D005434:Flow Cytometry / Q000379:methods; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis; D013154:Spleen / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007371:Interferon-gamma; C067980:CD68 antigen, human; D000097382:CD68 Molecule