Successful induction of adjuvant arthritis in mice by treatment with a monoclonal antibody against IL-4

Adjuvant arthritis (AA) is an experimental model of autoimmune disease in r ats induced by immunization with Mycobacterium tuberculosis (MT), Induction of AA in other species, including mice, has been shown to be difficult, In the present study, we found that AA could be induced in mice if the animal s were treated with a mAb (11B11 mAb) against IL-4, Histologically, the joi nts exhibited synovial edema with infiltration of many neutrophils in the e arly phase of inflammation. In its late phase, there were proliferation of synovium, cell infiltrate in which mononuclear cells predominated, and dest ruction of cartilage and subchondral bone. The joint inflammation was passi vely transferred to normal syngeneic recipient mice with lymphoid cells but not with sera from mice immunized with MT followed by treatment with the a nti-IL-4 Ab, Delayed-type hypersensitivity (DTH) and proliferative response s of lymphoid cells to purified protein derivative were markedly augmented in 11R11 mab-treated mice. Furthermore, the induction of arthritis was asso ciated with a marked decrease in IL-4 secretion but a significant increase in IFN-gamma and IL-2 production. Thus, the neutralization of IL-4 by an an ti-IL-4 Ab appears to be required For the induction of AA in mice.