Effect of a Monoclonal Antibody against Interleukin-4 on Suppression of Antigen-Induced Arthritis in Mice by Oral Administration of the Inducing Antigen

Abstract

We investigated a role for interleukin-4 (IL-4) in suppression of T-cell-mediated antigen-induced arthritis (AIA) in mice by oral administration of the inducing antigen. For this investigation, a monoclonal antibody (11B11 mAb) that specifically neutralizes IL-4 was employed. AIA was induced by immunization with methylated bovine serum albumin (mBSA) (day 0) followed by intraarticular injection of mBSA into the ankle joint. To induce oral tolerance, mBSA was administered orally once a day from days −5 to −1. The 11B11 mAb was injected ip 30 min before each oral administration of mBSA. Oral administration of mBSA resulted in marked suppression of AIA. Suppression of the joint inflammation by the oral antigen was significantly diminished by treatment with 11B11 mAb. The mAb treatment was also followed by blockade of suppression of proliferative responses of lymphoid cells to mBSA by the oral antigen. Furthermore, secretion of IL-4 was significantly increased following oral administration of mBSA and the increased IL-4 secretion was markedly reduced by treatment with 11B11 mAb. There was a decrease in production of IFN-γ in orally tolerized mice that was blocked by the IL-4-neutralizing mAb. Thus, treatment with an anti-IL-4 mAb appears to be effective in blocking suppression of AIA by oral administration of the inducing antigen. The results also suggest that IL-4 may play a role in downregulation of T-cell-mediated inflammation by feeding pathogenic antigens.