{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:11:55Z","timestamp":1787731915603,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:00:00Z","timestamp":1372723200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Macrophage activation syndrome (MAS) is a devastating cytokine storm syndrome complicating many inflammatory diseases and characterized by fever, pancytopenia, and systemic inflammation. It is clinically similar to hemophagocytic lymphohistiocytosis (HLH), which is caused by viral infection of a host with impaired cellular cytotoxicity. Murine models of MAS and HLH illustrate that interferon\u2010\u03b3 (IFN\u03b3) is the driving stimulus for hemophagocytosis and immunopathology. This study was undertaken to investigate the inflammatory contributors to a murine model of Toll\u2010like receptor 9 (TLR\u20109)\u2013induced fulminant MAS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type, transgenic, and cytokine\u2010inhibited mice were treated with an IL\u201010 receptor blocking antibody and a TLR\u20109 agonist, and parameters of MAS were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fulminant MAS was characterized by dramatic elevations in IFN\u03b3, IL\u201012, and IL\u20106 levels. Increased serum IFN\u03b3 levels were associated with enhanced IFN\u03b3 production within some hepatic cell populations but also with decreased numbers of IFN\u03b3\u2010positive cells. Surprisingly, IFN\u03b3\u2010knockout mice developed immunopathology and hemophagocytosis comparable to that seen in wild\u2010type mice. However, IFN\u03b3\u2010knockout mice did not become anemic and had greater numbers of splenic erythroid precursors. IL\u201012 neutralization phenocopied disease in IFN\u03b3\u2010knockout mice. Interestingly, type I IFNs contributed to the severity of hypercytokinemia and weight loss, but their absence did not otherwise affect MAS manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data demonstrate that both fulminant MAS and hemophagocytosis can arise independently of IFN\u03b3, IL\u201012, or type I IFNs. They also suggest that IFN\u03b3\u2010mediated dyserythropoiesis, not hemophagocytosis, is the dominant cause of anemia in fulminant TLR\u20109\u2013induced MAS. Thus, our data establish a novel mechanism for the acute anemia of inflammation, but suggest that a variety of triggers can result in hemophagocytic disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37958","type":"journal-article","created":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T19:39:02Z","timestamp":1364845142000},"page":"1764-1775","source":"Crossref","is-referenced-by-count":114,"title":["Interferon\u2010\u03b3 Mediates Anemia but Is Dispensable for Fulminant Toll\u2010like Receptor 9\u2013Induced Macrophage Activation Syndrome and Hemophagocytosis in Mice"],"prefix":"10.1002","volume":"65","author":[{"given":"Scott W.","family":"Canna","sequence":"first","affiliation":[{"name":"The Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wrobel","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niansheng","family":"Chu","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Portia A.","family":"Kreiger","sequence":"additional","affiliation":[{"name":"A. 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