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

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 Journal of Immunology, 2009, 182: 7272-7279.