PMID- 16519734
OWN - NLM
STAT- MEDLINE
DCOM- 20060721
LR  - 20180822
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 84
IP  - 2
DP  - 2006 Apr
TI  - IL-18 is redundant in T-cell responses and in joint inflammation in 
      antigen-induced arthritis.
PG  - 166-73
AB  - 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.
FAU - Santos, Leilani L
AU  - Santos LL
AD  - Centre for Inflammatory Diseases, Monash Institute of Medical Research, Monash 
      Medical Centre, Melbourne, Australia. lanie.santos@med.monash.edu.au
FAU - Milenkovski, Georgia P
AU  - Milenkovski GP
FAU - Hall, Pamela H
AU  - Hall PH
FAU - Leech, Michelle
AU  - Leech M
FAU - Sharma, Laveena
AU  - Sharma L
FAU - Takeda, Kiyoshi
AU  - Takeda K
FAU - Akira, Shizuo
AU  - Akira S
FAU - Kitching, A Richard
AU  - Kitching AR
FAU - Morand, Eric F
AU  - Morand EF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Animals
MH  - Antibody Formation/genetics/immunology
MH  - Arthritis, Experimental/genetics/*immunology/pathology
MH  - Autoantibodies/immunology
MH  - Autoantigens/immunology
MH  - Cytokines/genetics/immunology
MH  - Hypersensitivity, Delayed/genetics/immunology/pathology
MH  - Inflammation/immunology/pathology
MH  - Interleukin-18/genetics/*immunology
MH  - Lymphocyte Activation/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Species Specificity
MH  - Synovitis/genetics/immunology/pathology
MH  - Th1 Cells/*immunology/pathology
EDAT- 2006/03/08 09:00
MHDA- 2006/07/22 09:00
CRDT- 2006/03/08 09:00
PHST- 2006/03/08 09:00 [pubmed]
PHST- 2006/07/22 09:00 [medline]
PHST- 2006/03/08 09:00 [entrez]
AID - ICB [pii]
AID - 10.1111/j.1440-1711.2005.01406.x [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2006 Apr;84(2):166-73. doi: 10.1111/j.1440-1711.2005.01406.x.