IL-18 is redundant in T-cell responses and in joint inflammation in antigen-induced arthritis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-04

AUTHORS

Leilani L Santos, Georgia P Milenkovski, Pamela H Hall, Michelle Leech, Laveena Sharma, Kiyoshi Takeda, Shizuo Akira, A Richard Kitching, Eric F Morand

ABSTRACT

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. More... »

PAGES

icb200622

Identifiers

URI

http://scigraph.springernature.com/pub.10.1111/j.1440-1711.2005.01406.x

DOI

http://dx.doi.org/10.1111/j.1440-1711.2005.01406.x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001793426

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16519734


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