| First Author | Santos LL | Year | 2006 |
| Journal | Immunol Cell Biol | Volume | 84 |
| Issue | 2 | Pages | 166-73 |
| PubMed ID | 16519734 | Mgi Jnum | J:105836 |
| Mgi Id | MGI:3616745 | Doi | 10.1111/j.1440-1711.2005.01406.x |
| Citation | Santos LL, et al. (2006) IL-18 is redundant in T-cell responses and in joint inflammation in antigen-induced arthritis. Immunol Cell Biol 84(2):166-73 |
| abstractText | Summary IL-18 is an important cofactor in Th1 immune responses and it has additional roles in inflammation. Recent reports suggest the contribution of IL-18 to immune responses may vary between mouse strains and immune contexts. We investigated the contribution of IL-18 to T-cell activation and joint inflammation in Ag-induced arthritis (AIA) in C57Bl/6 mice. AIA and cutaneous delayed-type hypersensitivity (DTH) reactions were induced in wild-type (WT) and IL-18(-/-) C57Bl/6 mice, and Ag-specific T-cell proliferation and IFN-gamma and IL-4 production were measured. The humoral immune response was measured as serum antibody to the disease-initiating Ag, methylated BSA (mBSA). Splenocyte production of IL-6 was measured by ELISA. To confirm the dependence of this model on Th1-cell-mediated immunity, IL-12p40(-/-) mice were similarly studied. WT mice developed synovitis, joint effusion, cartilage destruction and bone damage associated with induction of DTH, and in vitro Ag-specific T-cell proliferation and IFN-gamma production. Unexpectedly, IL-18(-/-) mice developed AIA and indices of T-cell activation were similar to those of WT mice. In contrast, IL-12p40(-/-) mice did not develop AIA, DTH or T-cell activation. WT and IL-18(-/-) mice, but not IL-12p40(-/-) mice, developed significantly increased serum antibody to mBSA compared with naive controls. WT and IL-18(-/-) splenocytes produced high levels of IL-6, whereas IL-12p40(-/-) cells had significantly lower IL-6 production compared with both. In conclusion, IL-18 is redundant both as a Th1 response cofactor and inflammatory cytokine, whereas IL-12p40(-/-) is a key cytokine, in AIA in C57Bl/6 mice. |
