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The Journal of Immunology, 2009, 182, 7272 -7279
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0803497
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Recombinant Soluble Human Fc{gamma}R1A (CD64A) Reduces Inflammation in Murine Collagen-Induced Arthritis1

Jeff L. Ellsworth2,*, Nels Hamacher{dagger}, Brandon Harder*, Ken Bannink{ddagger}, Thomas R. Bukowski{dagger}, Kelly Byrnes-Blake{ddagger}, Sara Underwood{ddagger}, Colleen Oliver{ddagger}, Kimberly S. Waggie{ddagger}, Claire Noriega{dagger}, LuAnne Hebb§, Mark W. Rixon{dagger} and Katherine E. Lewis*

* Department of Immunology, {dagger} Department of Protein Biochemistry, {ddagger} Department of Pre-Clinical Development, and § Department of Bio-Process Development, ZymoGenetics, Seattle, WA 98102

Binding of immune complexes to cellular Fc{gamma}Rs can promote cell activation and inflammation. In previous studies, a recombinant human (rh) soluble Fc{gamma}R, rh-Fc{gamma}RIA (CD64A), was shown to block inflammation in passive transfer models of immune complex-mediated disease. To assess whether rh-Fc{gamma}RIA could block inflammation in a T cell- and B cell-dependent model of immune complex-mediated disease, the efficacy of rh-Fc{gamma}RIA in collagen-induced arthritis was evaluated. Mice with established arthritis were treated with a single s.c. injection of rh-Fc{gamma}RIA (0.2–2.0 mg/dose) given every other day for 11 days. Relative to mice injected with vehicle alone, mice treated with rh-Fc{gamma}RIA 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{gamma}RIA-treated mice and occurred in the presence of a significant murine Ab response to rh-Fc{gamma}RIA. Comparison of the serum rh-Fc{gamma}RIA concentration vs time profiles for rh-Fc{gamma}RIA administered at two dose levels by i.v. and s.c. injection revealed that the bioavailabilty of s.c. administered rh-Fc{gamma}RIA was 27–37%. Taken together, these data show that rh-Fc{gamma}RIA is an effective inhibitor of inflammation in a model of established arthritis in mice.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported in its entirety by ZymoGenetics.

2 Address correspondence and reprint requests to Dr. Jeff L. Ellsworth, Department of Immunology, ZymoGenetics, 1201 Eastlake Avenue East, Seattle, WA 98102. E-mail address: jefe{at}zgi.com

3 Abbreviations used in this paper: IC, immune complexes; CHO, Chinese hamster ovary; rh, recombinant human; CIA, collagen-induced arthritis; AUC, area under the concentration vs time curve; CV, column volume.






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