High doses of interleukin‐12 inhibit the development of joint disease in DBA/1 mice immunized with type II collagen in complete Freund's adjuvant

Abstract

Abstract Collagen‐induced arthritis (CIA) is an (autoimmune) joint disease readily elicited in DBA/1 mice by immunization with type II collagen (CII) emulsified with complete Freund's adjuvant. It is a destructive arthritis involving about 50% of the limbs and occurs with an incidence of 70% to 100%. In this study we evaluated the effect of mouse recombinant interleukin‐12 (mrIL‐12) on CIA. Administration of mrIL‐12 at high doses (1 μg/mouse, daily) for 2 or 3 weeks delayed the onset and reduced the incidence of CIA. Furthermore, the severity of CIA was much milder and in most cases restricted to single digits of the paws. Short‐term administration of high doses of IL‐12 exerted some, but less pronounced, disease‐suppressing effect. In contrast, 10‐fold lower doses of IL‐12 given during the first 3 weeks, or high doses of IL‐12 administered therapeutically proved to be ineffective. Only those regimens of IL‐12 treatment that ameliorated CIA were associated with a down‐regulation of the CII‐specific antibody response. A strong inhibition of CII‐specific IgG1 antibodies (10‐ to 20‐fold) and a moderately (2‐ to 6‐fold) suppressed IgG2b response was observed, whereas the level of CII‐specific IgG2a antibodies remained high. Taken together, the results indicate that some initial events in the induction of CIA in DBA/1 mice injected with CII emulsified with CFA are suppressed by treatment with high doses of IL‐12.