Protective major histocompatibility complex genes and the role of interleukin‐4 in collagen‐induced arthritis

Abstract

To investigate the role of interleukin (IL)‐4 during the triggering of collagen‐induced arthritis, we examined the effects of the I‐A^b and I‐E protective/suppressive genes and passively administered anti‐IL‐4 monoclonal antibody. In contrast to the action of I‐E expression on its own, which has mainly a suppressive effect post‐triggering, the combination of I‐A^b and I‐E had a marked protective effect. Assuming, on the basis of previous experience with the I‐A^b allele, that it might act through suppressing early IL‐4 production, we treated mice with the 11B11 IL‐4‐neutralizing antibody around the time of initial immunization with collagen. Treatment over a period extending to 6 days post‐immunization exacerbated the arthritis, but when curtailed to 2 days post‐immunization (and tested in pristane‐primed animals), the disease was reduced. We conclude that IL‐4 plays an essential role in triggering the disease.