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.
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.
Hess
H
H
Institut für Immunologie, Mainz, Germany.
Gately
M K
MK
Rüde
E
E
Schmitt
E
E
Szeliga
J
J
Germann
T
T
D000818:Animals; D001169:Arthritis, Experimental / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D001323:Autoantibodies / Q000096:biosynthesis / Q000187:drug effects; D003094:Collagen; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005620:Freund's Adjuvant; D015994:Incidence; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
D001323:Autoantibodies; D018664:Interleukin-12; D003094:Collagen; D005620:Freund's Adjuvant