| First Author | Matthys P | Year | 1998 |
| Journal | Eur J Immunol | Volume | 28 |
| Issue | 7 | Pages | 2143-51 |
| PubMed ID | 9692883 | Mgi Jnum | J:49316 |
| Mgi Id | MGI:1277321 | Doi | 10.1002/(SICI)1521-4141(199807)28:07<2143::AID-IMMU2143>3.0.CO;2-C |
| Citation | Matthys P, et al. (1998) Anti-IL-12 antibody prevents the development and progression of collagen-induced arthritis in IFN-gamma receptor-deficient mice. Eur J Immunol 28(7):2143-51 |
| abstractText | In several models of inflammation, including collagen-induced arthritis (CIA), the disease-promoting effect of IL-12 has been attributed to its well-known ability to produce IFN-gamma. However, IFN-gamma receptor knockout (IFN-gammaR KO) mice of the DBA/1 strain have been reported to be more susceptible to CIA than corresponding wild-type mice, indicating the existence of an IFN-gamma-mediated protective pathway in this model. In the present study the development of CIA was found to be completely prevented by pretreatment with a neutralizing anti-IL-12 antibody, not only in wild-type, but significantly also in IFN-gammaR KO mice. In both strains of mice, the protective effect of anti-IL-12 was associated with lower production of anti-collagen type II antibodies. In vivo stimulation with anti-CD3 antibody in arthritic IFN-gammaR KO mice resulted in production of higher levels of circulating IFN-gamma, TNF and IL-2 than in corresponding control mice that had not received the arthritis-inducing immunization. This was not the case in arthritis-developing wild-type mice. Furthermore, the protective effect of anti-IL-12 antibody in mutant, but not in wild-type mice, was associated with lower circulating IFN-gamma, TNF and IL-2 and higher IL-4 and IL-5 cytokine levels following an anti-CD3 challenge. The data indicate that IL-12 promotes the development of arthritis independently of its ability to induce or favor production of IFN-gamma. In fact, any IFN-gamma produced in the course of the disease process rather exerts a protective effect. Furthermore, our study suggests that, in the absence of a functional IFN-gamma system, endogenous IL-12 exerts its disease- promoting effect by favoring production of other Th1-associated cytokines (IL-2 and TNF), by inhibiting development of IL-4- and IL-5-producing T cells and by stimulating production of anti-collagen autoantibodies. |
