Susceptibility to collagen-induced arthritis: Cytokine-mediated regulation

Collagen-induced arthritis is an animal model of inflammatory polyarthritis that is induced in susceptible strains of rats and mice by intradermal imm unization with heterologous type II collagen emulsified in complete Freund' s adjuvant. Previous studies have demonstrated that disease induction is hi ghly MHC-restricted, with only mice of H-2(q) or H-2(r) haplotypes being su sceptible. We have used a panel of both susceptible and resistant strains o f mice in which either IFN-gamma or IL-10 signaling has been abolished by g ene deletion and show that disease can be readily induced in several resist ant strains of the H-2(b) and H-2(d) haplotype; susceptibility was highly d ependent on IL-12. IL-4 was also shown to be crucial for disease induction in this model. These results suggest that both Th1 and Th2 cytokines may be important in the etiopathogenesis of disease and that disease susceptibili ty may be a function of a dysregulated cytokine environment. (C) 2000 Acade mic Press.