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

Eur J Immunol. 1996 Jan;26(1):187-91. doi: 10.1002/eji.1830260129.


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 micrograms/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.

MeSH terms

  • Animals
  • Arthritis, Experimental / epidemiology
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / prevention & control*
  • Autoantibodies / biosynthesis
  • Autoantibodies / drug effects
  • Collagen*
  • Dose-Response Relationship, Immunologic
  • Drug Administration Schedule
  • Freund's Adjuvant*
  • Incidence
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred DBA


  • Autoantibodies
  • Interleukin-12
  • Collagen
  • Freund's Adjuvant