{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T09:56:05Z","timestamp":1760608565871,"version":"3.40.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Binding of immune complexes to cellular Fc\u03b3Rs can promote cell activation and inflammation. In previous studies, a recombinant human (rh) soluble Fc\u03b3R, rh-Fc\u03b3RIA (CD64A), was shown to block inflammation in passive transfer models of immune complex-mediated disease. To assess whether rh-Fc\u03b3RIA could block inflammation in a T cell- and B cell-dependent model of immune complex-mediated disease, the efficacy of rh-Fc\u03b3RIA in collagen-induced arthritis was evaluated. Mice with established arthritis were treated with a single s.c. injection of rh-Fc\u03b3RIA (0.2\u20132.0 mg\/dose) given every other day for 11 days. Relative to mice injected with vehicle alone, mice treated with rh-Fc\u03b3RIA exhibited lower serum concentrations of IL-6, anti-type II collagen Abs, and total IgG2a. These changes were correlated with lower levels of paw swelling and joint damage in the rh-Fc\u03b3RIA-treated mice and occurred in the presence of a significant murine Ab response to rh-Fc\u03b3RIA. Comparison of the serum rh-Fc\u03b3RIA concentration vs time profiles for rh-Fc\u03b3RIA administered at two dose levels by i.v. and s.c. injection revealed that the bioavailabilty of s.c. administered rh-Fc\u03b3RIA was 27\u201337%. Taken together, these data show that rh-Fc\u03b3RIA is an effective inhibitor of inflammation in a model of established arthritis in mice.<\/jats:p>","DOI":"10.4049\/jimmunol.0803497","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T21:00:29Z","timestamp":1242766829000},"page":"7272-7279","source":"Crossref","is-referenced-by-count":25,"title":["Recombinant Soluble Human Fc\u03b3R1A (CD64A) Reduces Inflammation in Murine Collagen-Induced Arthritis"],"prefix":"10.1093","volume":"182","author":[{"given":"Jeff L","family":"Ellsworth","sequence":"first","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nels","family":"Hamacher","sequence":"additional","affiliation":[{"name":"Department of Protein Biochemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Bannink","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R","family":"Bukowski","sequence":"additional","affiliation":[{"name":"Department of Protein Biochemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Byrnes-Blake","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly S","family":"Waggie","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Noriega","sequence":"additional","affiliation":[{"name":"Department of Protein Biochemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LuAnne","family":"Hebb","sequence":"additional","affiliation":[{"name":"Department of Bio-Process Development , ZymoGenetics, Seattle, WA 98102"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W","family":"Rixon","sequence":"additional","affiliation":[{"name":"Department of Protein Biochemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine E","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,6,1]]},"reference":[{"key":"2025032715455838800_R1","first-page":"798","article-title":"Fc receptors are major mediators of antibody based inflammation in autoimmunity.","volume-title":"Curr. 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Med.","year":"2004"},{"key":"2025032715455838800_R12","first-page":"407","article-title":"The genetic and immunopathological processes underlying collagen-induced arthritis.","volume-title":"Immunology","year":"2001"},{"key":"2025032715455838800_R13","first-page":"189","article-title":"An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen.","volume-title":"J. Immunol. Methods","year":"2005"},{"key":"2025032715455838800_R14","first-page":"481","article-title":"Resistance to development of collagen-induced arthritis in C57BL\/6 mice is due to a defect in secondary, but not in primary, immune response.","volume-title":"J. Clin. Immunol.","year":"2004"},{"key":"2025032715455838800_R15","first-page":"3","article-title":"Immunopathogenesis of collagen arthritis.","volume-title":"Springer Semin. Immunopathol.","year":"2003"},{"key":"2025032715455838800_R16","first-page":"666","article-title":"Immunisation against heterologous type II collagen induces arthritis in mice.","volume-title":"Nature","year":"1980"},{"key":"2025032715455838800_R17","first-page":"507","article-title":"Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA).","volume-title":"Clin. Exp. Immunol.","year":"1997"},{"key":"2025032715455838800_R18","first-page":"1109","article-title":"Association of the course of collagen-induced arthritis with distinct patterns of cytokine and chemokine messenger RNA expression.","volume-title":"Arthritis Rheum.","year":"1999"},{"key":"2025032715455838800_R19","first-page":"485","article-title":"Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA).","volume-title":"Clin. Exp. 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Pharmacother.","year":"2004"},{"key":"2025032715455838800_R24","first-page":"454","article-title":"Complement deficiency ameliorates collagen-induced arthritis in mice.","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032715455838800_R25","first-page":"4340","article-title":"A role for complement in antibody-mediated inflammation: C5-deficient DBA\/1 mice are resistant to collagen-induced arthritis.","volume-title":"J. Immunol.","year":"2000"},{"key":"2025032715455838800_R26","first-page":"339","article-title":"Impaired immune and acute-phase responses in interleukin-6-deficient mice.","volume-title":"Nature","year":"1994"},{"key":"2025032715455838800_R27","first-page":"S4","article-title":"Interleukin-6 and rheumatic diseases.","volume-title":"Arthritis Res. Ther.","year":"2006"},{"key":"2025032715455838800_R28","first-page":"461","article-title":"Interleukin 6 is required for the development of collagen-induced arthritis.","volume-title":"J. Exp. 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Immunol.","year":"1990"},{"key":"2025032715455838800_R44","first-page":"89","article-title":"Human antibody-Fc receptor interactions illuminated by crystal structures.","volume-title":"Nat. Rev. Immunol.","year":"2004"},{"key":"2025032715455838800_R45","first-page":"154","article-title":"Treatment of lupus-prone NZB\/NZW F1 mice with recombinant soluble Fc\u03b3 receptor II (CD32).","volume-title":"Ann. Rheum. Dis.","year":"2008"},{"key":"2025032715455838800_R46","first-page":"894","article-title":"Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with Fc\u03b3 receptors and can be effectively blocked by decoy Fc\u03b3 receptors.","volume-title":"Blood","year":"2008"},{"key":"2025032715455838800_R47","first-page":"225","article-title":"Amelioration of collagen-induced arthritis by human recombinant soluble Fc\u03b3RIIb.","volume-title":"Clin. 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