Enhancement of T-Cell-Mediated Arthritis in Mice by Treatment with a Monoclonal Antibody against Interleukin-4

Abstract

We investigated a role for interleukin-4 (IL-4) in T-cell-mediated arthritis by employing a monoclonal antibody against IL-4 (11B11 mAb). As a model of T-cell-mediated arthritis, antigen-induced arthritis (AIA) in mice was used. To induce AIA, mice were immunized with methylated bovine serum albumin (mBSA) (day 0). On day 14, the animals were intraarticularly injected with mBSA into the ankle joint. 11B11 mAb was daily injected ip for a period of 10 days, commencing on the day of immunization with mBSA. We found that treatment with 11B11 mAb significantly enhanced the severity of AIA. The enhanced arthritis was also observed in mice injected iv with lymphoid cells from mBSA-immunized mice, followed by the intraarticular challenge injection of mBSA. The enhancement of AIA by the anti-IL-4 mAb was associated with a significant increase in the proliferative response of lymphoid cells to mBSA in mice treated with the mAb. The secretion of IL-4 as well as IL-5 decreased in 11B11 mAb-treated mice, while the production of IFN-γ and IL-2 increased following mAb treatment. Thus, the neutralization of IL-4 by an anti-IL-4 mAb appeared to enhance AIA, suggesting a role for IL-4 in downregulating T-cell-mediated joint inflammation.