Recombinant Soluble Human FcγR1A (CD64A) Reduces Inflammation in Murine Collagen-Induced Arthritis | Zendy

Jeff L. Ellsworth | Zendy; Nels Hamacher | Zendy; Brandon Harder | Zendy; K. Bannink | Zendy; Thomas R. Bukowski | Zendy; Kelly Byrnes-Blake | Zendy; Sara Underwood | Zendy; Colleen Oliver | Zendy; Kimberly S. Waggie | Zendy; Claire Noriega | Zendy; LuAnne Hebb | Zendy; Mark W. Rixon | Zendy; Katherine E. Lewis | Zendy

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Recombinant Soluble Human FcγR1A (CD64A) Reduces Inflammation in Murine Collagen-Induced Arthritis

Author(s) -

Jeff L. Ellsworth,

Nels Hamacher,

Brandon Harder,

K. Bannink,

Thomas R. Bukowski,

Kelly Byrnes-Blake,

Sara Underwood,

Colleen Oliver,

Kimberly S. Waggie,

Claire Noriega,

LuAnne Hebb,

Mark W. Rixon,

Katherine E. Lewis

Publication year - 2009

Publication title -

the journal of immunology

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.0803497

Subject(s) - inflammation , arthritis , immune system , chemistry , immune complex , pharmacology , medicine , recombinant dna , antibody , endocrinology , immunology , biochemistry , gene

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

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