HIGH-DOSES OF INTERLEUKIN-12 INHIBIT THE DEVELOPMENT OF JOINT DISEASEIN DBA 1 MICE IMMUNIZED WITH TYPE-II COLLAGEN IN COMPLETE FREUNDS-ADJUVANT/

Collagen-induced arthritis (CIA) is an (autoimmune) joint disease read ily elicited in DBA/1 mice by immunization with type II collagen (CII) emulsified with complete Freund's adjuvant. It is a destructive arthr itis in olving about 50 % of the limbs and occurs with an incidence of 70 % to 100 %. In this study we evaluated the effect of mouse recombi nant interleukin-12 (mrIL-12) on CIA. Administration of mrIL-12 at hig h doses (1 mu g/mouse, daily) for 2 or 3 weeks delayed the onset and r educed the incidence of CIA. Furthermore, the severity of CIA was much milder and in most cases restricted to single digits of the paws. Sho rt-term administration of high doses of IL- 12 exerted some, but less pronounced, disease-suppressing effect. In contrast, 10-fold lower dos es of IL-12 given during be first 3 weeks, or high doses of IL-12 admi nistered therapeutically proved to he ineffective. Only those regimens of IL-12 treatment that ameliorated CIA were associated with a down-r egulation of the CII-specific antibody response. A strong inhibition o f CII-specific IgG1 antibodies (10- to 20-fold) and a moderately (2- t o 6-fold) suppressed IgG2b response was observed, whereas the level of CII-specific IgG2a antibodies remained high. Taken together, the resu lts indicate that some initial events in the induction of CIA in DBA/1 mice injected with CII emulsified with CFA, are suppressed hy treatme nt with high doses of IL-12.