Recombinant soluble human FcgammaR1A (CD64A) reduces inflammation in murine collagen-induced arthritis.
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.
Ellsworth
Jeff L
JL
Department of Immunology, Zymo-Genetics, Seattle, WA 98102, USA. jefe@zgi.com
Hamacher
Nels
N
Harder
Brandon
B
Bannink
Ken
K
Bukowski
Thomas R
TR
Byrnes-Blake
Kelly
K
Underwood
Sara
S
Oliver
Colleen
C
Waggie
Kimberly S
KS
Noriega
Claire
C
Hebb
LuAnne
L
Rixon
Mark W
MW
Lewis
Katherine E
KE
D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D010599:Pharmacokinetics; D017452:Receptors, IgG / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins; D012995:Solubility; D016896:Treatment Outcome
D000906:Antibodies; C485701:Fcgr1 protein, mouse; D007074:Immunoglobulin G; D015850:Interleukin-6; D017452:Receptors, IgG; D011994:Recombinant Proteins; D003094:Collagen