Influenza virus host response of C57Bl/6 mice treated with TACI-Ig.
TACI-Ig is a soluble glycoprotein comprised of a human IgG1-Fc fused with the extracellular domain of the human TACI receptor. Chronic exposure to TACI-Ig is associated with reduced circulating B cells in mouse and non-human primates, and a concomitant decrease in circulating immunoglobulin. Because of these activities, TACI-Ig is in clinical evaluation for treatment of various autoimmune diseases and B cell malignancies. In this study, the effect of TACI-Ig treatment on the ability of C57Bl/6 mice to clear influenza virus was evaluated. C57Bl/6 mice were exposed to vehicle (negative control), dexamethasone (positive control), or TACI-Ig (0.05, 0.50, or 5.0 mg/kg, SC, thrice weekly) from within one week prior to viral exposure through 21 days thereafter. Dexamethasone treatment of influenza-infected mice prolonged the infection, and decreased survival, body weight, lymphoid organ weight, influenza-specific IgM and IgG, and viral clearance relative to control animals, consistent with its expected immunosuppressive activity. Animals treated with TACI-Ig (0.05, 0.50, and 5.0 mg/kg) demonstrated a dose-dependent decrease in spleen weight and influenza-specific IgG and IgM in both lung and serum relative to control animals. In addition, flow cytometric analyses showed a decrease in B cells, but not T cells, in peripheral blood in animals treated with TACI-Ig. However, neither viral clearance nor survival was affected by TACI-Ig treatment. These data demonstrate the expected B cell-specific pharmacological effects of TACI-Ig in influenza-challenged C57Bl/6 mice without apparent effect on influenza virus clearance. It is concluded that non-B cell related antiviral competence remains intact during TACI-Ig treatment.
Roque
R
R
ZymoGenetics Inc, Seattle, WA 98102, USA. rroq@zgi.com
Ponce
R
R
Burleson
F
F
Cabrit
M
M
Broly
H
H
Rogge
M
M