IL-18 is redundant in T-cell responses and in joint inflammation in antigen-induced arthritis
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2006 |
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| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
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| Enthalten in: |
Immunology and cell biology - 84(2006), 2 vom: 15. Apr., Seite 166-73 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Santos, Leilani L [VerfasserIn] |
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| Themen: |
Autoantibodies |
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| Anmerkungen: |
Date Completed 21.07.2006 Date Revised 22.08.2018 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM161109616 |
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| 100 | 1 | |a Santos, Leilani L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IL-18 is redundant in T-cell responses and in joint inflammation in antigen-induced arthritis |
| 264 | 1 | |c 2006 | |
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| 500 | |a Date Completed 21.07.2006 | ||
| 500 | |a Date Revised 22.08.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Autoantibodies |2 NLM | |
| 650 | 7 | |a Autoantigens |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Interleukin-18 |2 NLM | |
| 700 | 1 | |a Milenkovski, Georgia P |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Pamela H |e verfasserin |4 aut | |
| 700 | 1 | |a Leech, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Laveena |e verfasserin |4 aut | |
| 700 | 1 | |a Takeda, Kiyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Akira, Shizuo |e verfasserin |4 aut | |
| 700 | 1 | |a Kitching, A Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Morand, Eric F |e verfasserin |4 aut | |
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